Multiple Myloma

[heading] FOCUS POINTS [/heading]

Multiple Myeloma (MM)

Definition & Pathophysiology

  • Malignant proliferation of plasma cells in the bone marrow.
  • Produces monoclonal immunoglobulin (M-protein) or light chains.
  • Leads to bone destruction, renal impairment, anemia, and immunodeficiency.

Diagnostic criteria (IMWG 2014):

  • ≥10% clonal plasma cells plus:
    • CRAB: hyperCalcemia, Renal dysfunction, Anemia, Bone lesions
    • OR SLiM biomarkers: ≥60% plasma cells, FLC ratio ≥100, >1 focal lesion on MRI.

Clinical Features

  • Bone pain, fractures, lytic lesions
  • Hypercalcemia (stones, groans, bones)
  • Renal impairment (cast nephropathy, light-chain deposition)
  • Anemia, infections (immunosuppression)

Risk Stratification

Treatment Overview

Goal: disease control, prolong survival, improve QoL (not curative).

1. Initial Therapy (Transplant-Eligible)

2. Initial Therapy (Transplant-Ineligible)

3. Relapsed/Refractory MM

Supportive Care (High Yield for Pharmacists)

Key Adverse Effects to Monitor

High-Yield Pharmacist Pearls

  • Always consider transplant eligibility before starting induction.
  • VRd is standard first-line (add daratumumab if available).
  • Lenalidomide maintenance post-ASCT improves PFS/OS.
  • Monitor for VTE with IMiDs, viral reactivation with PIs, and bone health in all patients.
  • New era: BCMA-targeted therapies (CAR-T, bispecifics) are changing relapsed/refractory MM management.

I. Disease Overview and Pre-Malignant States
Multiple myeloma is a plasma cell disorder defined by the accumulation of malignant clonal plasma cells in the bone marrow. It typically progresses from asymptomatic precursor states:

II. Diagnosis and Staging

Active MM is diagnosed when a patient has ≥ 10% BMPC (or a biopsy-proven plasmacytoma) plus one or more myeloma-defining events categorized by the "CRAB" and "SLiM" criteria:

  • CRAB Criteria: Calcium (> 11 mg/dL), Renal dysfunction (SCr > 2 mg/dL or CrCl < 40 mL/min), Anemia (Hgb < 10 g/dL), and Bone lesions.
  • SLiM Criteria: Sixty percent or more BMPC, involved: uninvolved free Light chain ratio ≥ 100, and MRI showing > 1 focal marrow lesion.

Staging and Risk Stratification:
Revised International Staging System (R-ISS): Incorporates ISS (albumin and beta-2 microglobulin) plus LDH and high-risk cytogenetics (del17p, t4;14, t14;16).
Second Revision (R2-ISS): Further refines risk by including chromosome 1q gain in the scoring system.
Cytogenetics: Deletion 17p and translocations t(4;14) and t(14;16) are associated with a poor prognosis, while t(11;14) is considered intermediate risk.

III. Primary Treatment Strategies

While MM remains incurable, triplet drug regimens are the standard of care as they improve response rates and survival compared to doublets.
Transplant-Eligible Patients: The common sequence is induction (3–4 cycles) followed by autologous stem cell transplant (ASCT) and maintenance.
Induction: VRd (Bortezomib, Lenalidomide, Dexamethasone) is a preferred Category 1 regimen. Monoclonal antibody quadruplets (e.g., Daratumumab + VRd) are increasingly used.
Non-Transplant Candidates: The goal is to reduce tumor burden and prolong survival. Preferred regimens include Dara-Rd (Daratumumab, Lenalidomide, Dex) and VRd.
Maintenance: Lenalidomide is the Category 1 preferred maintenance agent post-transplant due to demonstrated overall survival benefits. Doublet maintenance (e.g., Bortezomib/Lenalidomide) may be considered for high-risk patients.

IV. Relapsed/Refractory Disease

Treatment for relapsed disease depends on prior therapies and the duration of the previous response.

  • Early Relapse (1–3 prior lines): Preferred regimens include Daratumumab-based triplets (e.g., Dara-Kd or Dara-Rd) and Isatuximab-based triplets.
  • Late Relapse (> 3 prior lines): Newer modalities are utilized, including BCMA-targeted therapies like CAR-T cells (Idecabtagene vicleucel, Ciltacabtagene autoleucel) and bispecific T-cell engagers (Teclistamab, Elranatamab). Talquetamab, a GPRC5D-directed bispecific, is also used.

Management

Correct Answers

  1. D. BMPC=70%
  2. A. stage I
  3. D. Observation (Smoldering myeloma )
  4. d. Zoledronic acid 4 mg IV + calcitonin 4 IU/kg SubQ
  5. B. Enoxaparin 40 mg SubQ q12h (Prophylaxis: 0.5 mg/kg)
  6. C. Daratumumab, bortezomib, thalidomide, dexamethasone
  7. C. Daratumumab, bortezomib, lenalidomide, dexamethasone
  8. C. 1.3 mg/m2 SubQ D 1, 4, 8 and 11
  9. C. Carfilzomib, lenalidomide, dexamethasone (KRd) (relapsed)
  10. C. Daratumumab, carfilzomib, dexamethasone (Relapsed)
  11. A. Acyclovir
  12. A. Aspirin, acyclovir
  13. B. Pamidronate 90 mg IV over 4 hours
  14. B. Zoledronic acid 4 mg IV over 30 min
  15. D. Zoledronic acid 3 mg IV over 15 min every 4 weeks (CrCl of 35 mL/min)
  16. A. Zoledronic acid 4 mg IV once + calcitonin 4 IU/kg SubQ every 12 hours
  17. C. Denosumab 120 mg SubQ every 4 weeks
  18. A. Apixaban 2.5 mg twice daily
  19. A. Therapy with lenalidomide and dexamethasone (risk factors for DVT)
  20. D. Bortezomib, lenalidomide, dexamethasone
  21. C. Isatuximab, carfilzomib, dexamethasone
  22. D. Teclistamab
  23. B. Dexamethasone, acetaminophen, diphenhydramine
  24. B. Lenalidomide
  25. A. Aspirin 81 mg once daily (SAVED score <2)
  26. D. Enoxaparin 60 mg SubQ q12h Treatment: 1mg/kg)
  27. d. Clinical trials (relapsed 6 months after Auto SCT)
  28. c. Safe in renal failure (wrong)
  29. Thrombosis (Wrong)
  30. C Bone marrow biopsy. skeletal survey, B2 microglobulin (83%).
  31. A plasma cells (63% 7)
  32. B Hypercalcemia, renal failure, anemia, bone metastasis (69%)
[heading] EXAM QUESTIONS AND ANSWERS [/heading]

Which of the following is considered a diagnosis for multiple myeloma?

  • A. Serum monoclonal protein = 2 g/dl & BMPC=8%
  • B. Serum monoclonal protein = 4 g/dl, BMPC=30 % Ca=8 mg/dl, Hg=14 g/dl & Scr=0.8 mg/dl
  • C. FLCR= 1.8, Ca=10 mg/dl, Hg=12 g/dl & Scr=1.2 mg/dl
  • D. BMPC=70%

Answer: D. BMPC=70%

Explanation: The diagnosis of multiple myeloma requires specific criteria. One of the key "CRAB" features (Hypercalcemia, Renal insufficiency, Anemia, Bone lesions) must be present, or one of three specific biomarkers of malignancy (BMPC ≥60%, serum FLC ratio ≥100, or >1 focal lesion on MRI). Option D meets the diagnostic criterion of having ≥60% clonal plasma cells in the bone marrow (BMPC), even without any CRAB features. The other options do not meet the criteria: A has low protein and low BMPC (may be MGUS). B has high protein and BMPC but no CRAB features or biomarkers. C has abnormal values but none severe enough to be a CRAB feature or a biomarker.

NK is 55 years old patient who was diagnosed by MM, albumin=4g/dl,B2M=2.5 mg/l,LDH=220 U/l & cytogenetics test reveals triosomy 3, according to R-ISS what stage of disease this patient has ?

A. stage I
B. stage II
C. stage III
D. stage IV

Answer: A. stage I

Explanation: The Revised International Staging System (R-ISS) for multiple myeloma is calculated as follows:

  • Stage I: β2-microglobulin (B2M) < 3.5 mg/L and albumin ≥ 3.5 g/dL and normal LDH and absence of high-risk cytogenetics [del(17p), t(4;14), t(14;16)].
  • Stage III: B2M > 5.5 mg/L and either high-risk cytogenetics or high LDH.
  • Stage II: All cases not classified as I or III.
  • This patient has favorable markers: B2M=2.5 (<3.5), albumin=4.0 (≥3.5), and LDH=220 (normal). Trisomy 3 is not considered a standard high-risk cytogenetic abnormality. Therefore, the patient meets all criteria for R-ISS Stage I.

JM is a 54-year-old male with newly diagnosed monoclonal gammopathy of undetermined significance (MGUS). His baseline labs include SCr 0.80 mg/dL, calcium 8.6 mg/dL, Hgb 12.5 g/dL. According to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®), which of the following would be the most appropriate therapy for JM?

Correct answer is D. MGUS requires observation as it is a plasma cell proliferative disorder with a risk of progressing into smoldering and active MM; however, chemotherapy is reserved for the management of patients with active MM.

Answers A, B, and C are all treatment regimens reserved for patients with active MM and are not appropriate for a patient with MGUS.

JM has unfortunately progressed to active MM and presents to the urgent care center with lethargy and constipation. His labs are notable for calcium 10.9 mg/dL, SCr 2.6 mg/dL and albumin of 2.5 g/dL. In addition to aggressive hydration, which of the following interventions would be most appropriate for JM?

Answer D is correct.

  • Bisphosphonate therapy has been proven to reduce hypercalcemia of malignancy. The prescribing information for zoledronic acid recommends full dose zoledronic acid when used for management of hypercalcemia of malignancy up to a SCr 4.5 mg/dL. Additionally, the patient is symptomatic, so consideration should be given to calcitonin SubQ or IM to provide more rapid reduction in his calcium before the effect of bisphosphonate therapy in 48-96 hours.
  • Answer A is incorrect as the intranasal route for calcitonin is ineffective and not recommended for this indication.
  • Answer B is incorrect as loop diuretics should not be the only therapy provided to a symptomatic patient with hypercalcemia. They may be given to maintain aggressive hydration in addition to a bisphosphonate +/- calcitonin.
  • Answer C is incorrect as according to the guidelines and the prescribing information, zoledronic acid for hypercalcemia does not require a dose reduction in patients with SCr < 4.5 mg/dL.

Following JM’s initial presentation, he is incidentally found to have a lower extremity DVT. The medical team is planning for his discharge from the hospital including therapeutic anticoagulation. According to the NCCN Guidelines®, which of the following is the most appropriate treatment of DVT in anticipation of JM’s discharge from the hospital (78 kg, SCr 0.92, plt 38,000/mcL)?

The correct answer is B – enoxaparin dose should be adjusted to 0.5 mg/kg every 12 hours in the setting of mild thrombocytopenia (between 25-50,000/mcL).

  • Option A is incorrect because aspirin 325 mg would not be appropriate treatment for an acute DVT.
  • Option C is incorrect because enoxaparin 80 mg SubQ every 12 hours is full 1 mg/kg enoxaparin dosing and would put him at risk of bleeding complications in the setting of thrombocytopenia.
  • Option D is not appropriate as this is not the correct dosing for apixaban; however, apixaban may be used as an alternative to a LMWH for patients who refuse or have a compelling reason not to receive a LMWH. Data regarding dose adjustment for oral anticoagulants in the setting of thrombocytopenia is also limited.

AS is a 62-year-old female with newly diagnosed multiple myeloma. Her corrected calcium is 11.4 mg/dL, 40% plasma cells on bone marrow pathology, R-ISS stage III (β2M of 7.5 mg/L; high risk cytogenetics including del(17p), t(4;14)), and SCr 0.85. Eastern Cooperative Oncology Group (ECOG) status 0. She is eligible for autologous stem cell transplant and expresses interest in receiving induction therapy with a monoclonal antibody. Which of the following is the most appropriate first line treatment option for AS?

Correct answer is C

The only monoclonal antibody-based induction therapies recommended for transplant candidates are daratumumab + VTd (bortezomib, thalidomide, dexamethasone) as per the CASSIOPEIA trial, and daratumumab + VRd (bortezomib, lenalidomide, dexamethasone) as per the GRIFFIN trial.

  • Answer A: daratumumab, lenalidomide, and dexamethasone is an appropriate primary induction regimen for non-transplant candidates, as per the MAIA trial.
  • Answer B: elotuzumab, pomalidomide, and dexamethasone may be utilized in the relapsed and refractory setting as per the ELOQUENT-3 trial; however, neither elotuzumab nor pomalidomide are recommended in the frontline.
  • Answer D: isatuximab, pomalidomide, and dexamethasone may be utilized in the relapsed and refractory setting as per the ICARIA-MM trial; however, neither isatuximab nor pomalidomide are recommended in the frontline.

As is a 62-year-old female with newly diagnosed multiple myeloma. Her corrected calcium is 11.4 mg/dL, 40% plasma cells on bone marrow pathology, R-ISS stage III (β2M of 7.5 mg/L; high risk cytogenetics including del(17p), t(4;14)), and SCr 0.85. ECOG status 0. She is eligible for autologous stem cell transplant and will be starting primary induction therapy. Which of the following is the most appropriate first-line treatment option?

Answer: C. Daratumumab, bortezomib, lenalidomide, dexamethasone (D-VRd)

Explanation: For a transplant-eligible patient with newly diagnosed multiple myeloma (NDMM), a triplet regimen is the standard of care. For patients with high-risk cytogenetics (like this patient with del(17p) and t(4;14)), a four-drug regimen containing a proteasome inhibitor (bortezomib), an immunomodulatory drug (lenalidomide), a steroid (dexamethasone), and an anti-CD38 monoclonal antibody (daratumumab) is strongly recommended. The D-VRd regimen (option C) has shown superior efficacy in high-risk patients. Options A (doublet) and D (elotuzumab-based, which is less potent than daratumumab) are not optimal. Option B (DRd) is effective but is considered a standard-risk regimen; the addition of bortezomib is key for tackling high-risk disease.

AS is a pianist and concerned about peripheral neuropathy (PN). Following a discussion of potential options for induction therapy, AS inquires which of following bortezomib-based regimens is least likely to cause PN?

  • A. 1.3 mg/m2 IV D 1, 8, 15 and 22
  • B. 1.3 mg/m2 IV D 1, 4, 8 and 11
  • C. 1.3 mg/m2 SubQ D 1, 4, 8 and 11
  • D. 1.5 mg/m2 IV D 1, 8, 15 and 22

Correct answer is C. SubQ administration of bortezomib has exhibited reduced all grade peripheral neuropathy when compared to IV bortezomib.

Answers A, B, and D are all administered intravenously which has exhibited increased peripheral neuropathy when compared to SubQ administration. Patients who received weekly bortezomib vs administration on D 1,4, 8, and 11 experienced similar incidence of peripheral neuropathy; however, the total bortezomib dose per cycle was higher in the weekly group and they required fewer dose reductions.

AS has completed 4 cycles of daratumumab + VTd (bortezomib, thalidomide, dexamethasone), ASCT, and 2 consolidative cycles of daratumumab + VTd achieving a stringent complete response. Although recommended by her healthcare team, she chose to forego maintenance therapy following induction. She presents 2 years later with progressive disease and requires further therapy. Which of the following is the most appropriate therapy for AS at this time?

Correct Answer is C.

Carfilzomib, lenalidomide, dexamethasone (KRd) is a category 1 recommendation from the NCCN Guidelines for relapsed multiple myeloma.

Answers A, B, D are not preferred regimens by the NCCN Guidelines and there are other treatment options that would be more appropriate for AS at this time.

AS has completed 4 cycles of daratumumab + VRd (bortezomib, lenalidomide, dexamethasone), ASCT, and 2 consolidative cycles of daratumumab + VRd achieving a stringent complete response. She then continued lenalidomide maintenance until presenting 2 years later with progressive disease, now requiring further therapy. Which of the following is the most appropriate therapy for AS at this time?

Answer: C. Daratumumab, carfilzomib, dexamethasone (DKd)

Explanation: This patient is experiencing a relapse. A key principle in treating relapse is to use agents with a novel mechanism of action to which the patient is not likely to be resistant. This patient's initial therapy included daratumumab, bortezomib, and lenalidomide. Therefore, repeating VRd (option B) or using a similar regimen like VMP (option A) would be suboptimal due to potential resistance. Elotuzumab (option D) is less potent and often used in lenalidomide-sensitive patients. The best choice is a regimen containing carfilzomib, a next-generation proteasome inhibitor, combined with daratumumab (to which she may still be sensitive as it was used long ago) and dexamethasone. This provides two effective, novel agents compared to her initial therapy.

AS calls clinic and requests to speak with you regarding starting carfilzomib, lenalidomide, dexamethasone (KRd). She is inquiring about what supportive care medications she should start with therapy. She has an ECOG status 0 with no significant comorbidities or risk factors. In addition to venous thromboembolism (VTE) prophylaxis, which of the following do you recommend she start with the initiation of KRd?

  • A. Acyclovir
  • B. Valganciclovir and sulfamethoxazole/trimethoprim
  • C. Valacyclovir and posaconazole
  • D. No infectious prophylaxis needed

Correct Answer is A.

  • According to the NCCN Guidelines, all patients receiving therapy with a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib), daratumumab, or elotuzumab should receive antiviral prophylaxis (e.g., acyclovir, valacyclovir, or famciclovir) for prevention of herpes zoster reactivation.
  • Answer B is incorrect because although valganciclovir is active against herpes simplex virus (HSV) and varicella-zoster virus (VZV), it should be reserved for treatment and prophylaxis against cytomegalovirus (CMV); additionally, PJP prophylaxis is not required for therapy with carfilzomib, lenalidomide, and dexamethasone, although it may be considered in cases in which high doses of dexamethasone are utilized.
  • Answer C would not be appropriate as prophylaxis with posaconazole would not be warranted with this therapy unless the patient were to develop an invasive fungal infection in the setting of profound or prolonged neutropenia. Valacyclovir would be appropriate antiviral prophylaxis against HSV and VZV.
  • Answer D is incorrect as the NCCN Guidelines recommend that all patients receiving therapy with a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib), daratumumab, or elotuzumab should receive antiviral prophylaxis (e.g., acyclovir, valacyclovir, or famciclovir) for prevention of herpes zoster reactivation.

AS calls clinic and requests to speak with you regarding starting carfilzomib, lenalidomide, dexamethasone (KRd). She is inquiring about what supportive care medications she should start with therapy. She has an ECOG status 0 with no significant comorbidities or risk factors.

Which of the following do you recommend she start with the initiation of KRd?

  • A. Aspirin, acyclovir
  • B. Aspirin, sulfamethoxazole/trimethoprim
  • C. Aspirin, acyclovir, fluconazole
  • D. Aspirin

A. Aspirin, acyclovir

  • Correct Answer is A. The combination of lenalidomide with dexamethasone in the absence of additional patient specific risk factors warrants VTE prophylaxis with aspirin 81-325 mg daily.
  • Additionally, all patients receiving therapy with a proteasome inhibitor should receive antiviral prophylaxis for prevention of herpes zoster reactivation.
  • Answer B is incorrect as PIP prophylaxis is not recommended for therapy with carfilzomib, lenalidomide, and dexamethasone.
  • Answer C would not be appropriate as prophylaxis with fluconazole would not be warranted with this therapy unless the patient were to develop profound or prolonged neutropenia.
  • Answer D is incorrect as this option is lacking antiviral prophylaxis as is recommended per the NCCN Guidelines® for patients receiving proteasome inhibitors.

AS is now on cycle 2 of salvage therapy with KRd (carfilzomib, lenalidomide, dexamethasone). She received a bisphosphonate during her original induction therapy and now her oncologist would like to resume bone modifying therapy. Her CrCl is 85 mL/min. Which of the following do you recommend initiating at this time?

Answer B is the correct answer.

  • As per the NCCN Guidelines, all patients with active multiple myeloma, regardless of presence of lytic bone lesions, should receive bone modifying therapy with a bisphosphonate or denosumab. Pamidronate 90 mg IV over 4 hours is a recommended option as per both the ASCO and NCCN Guidelines.
  • Answer A is incorrect as zoledronic acid, in the setting of normal renal function, should be administered as 4 mg IV over at least 15 minutes.
  • Answers C and D are incorrect as denosumab should be administered as 120 mg SubQ injection; it should not be given intravenously, nor should it be given at a dose of 60 mg, which is the FDA approved dose marketed as Prolia® for osteoporosis. Denosumab 120 mg SubQ is preferred in patients with severe renal dysfunction.

AS is now on cycle 2 of salvage therapy with KRd (carfilzomib, lenalidomide, dexamethasone). She received a bisphosphonate during her original induction therapy and now her oncologist would like to resume bone modifying therapy. Her CrCl is 85 mL/min. Which of the following do you recommend initiating at this time?

Answer B. Zoledronic acid 4 mg IV over 30 min

  • Answer B is the correct answer. As per the NCCN Guidelines®, all patients with active multiple myeloma, regardless of presence of lytic bone lesions, should receive bone modifying therapy with a bisphosphonate or denosumab.
  • Answer A is incorrect as pamidronate should be administered as 90 mg over at least 2 hours.
  • Answers C and D are incorrect as denosumab should be administered as 120 mg SubQ injection.
  • This option is preferred in patients with severe renal dysfunction.

 

Upon initiating KRd (carfilzomib, lenalidomide, dexamethasone) for her relapsed multiple myeloma, AS was deemed to be at high risk of venous thromboembolism (VTE) due to her lenalidomide-based therapy, obesity, and prior history of VTE before her multiple myeloma diagnosis. She is not interested in injections and requests an oral medication for VTE prophylaxis. According to the SAVED and IMPEDE criteria, which of the following is most appropriate for AS?

  • A. Apixaban 2.5 mg twice daily
  • B. Aspirin 81 mg once daily
  • C. Rivaroxaban 20 mg once daily
  • D. Warfarin (INR 1.5-2.5)

Correct answer is A.

  • AS is deemed to be at high risk of VTE based on both the SAVED and IMPEDE scoring systems, as such prophylactic dose apixaban 2.5 mg twice daily would be appropriate. Alternatively, enoxaparin 40 mg SubQ daily, dalteparin 5,000 units SubQ daily, or warfarin (INR 2-3) may be appropriate.
  • Answer B is incorrect as aspirin 81 mg daily would be insufficient for someone at high risk of VTE, as per the SAVED and IMPEDE criteria.
  • Answer C is incorrect as rivaroxaban is currently not recommended for VTE prophylaxis in high risk multiple myeloma patients. The dose of 20 mg once daily is also not a standard prophylactic dose; 10 mg once daily may be appropriate prophylaxis for a high risk medical oncology (non-myeloma) patient.
  • Answer D is incorrect as warfarin may be used for high risk patients, but it should include a target INR of 2-3.

Upon initiating daratumumab,carfizomib,and dexamethasone for her relapsed multiple myeloma, AS was deemed to be at high risk of venous thromboembolism (VTE) due to her obesity and prior history of VTE before her multiple myeloma diagnosis.She is not interested in injections and requests an oral medication for VTE prophylaxis.According to the IMPEDE criteria, which of the following is most appropriate for AS?

  • A. Apixaban 2.5 mg twice daily
  • B. Aspirin 81 mg once daily
  • C. Rivaroxaban 20 mg once daily
  • D. Warfarin (INR 1.5-2.5)

Answer: A. Apixaban 2.5 mg twice daily

Explanation: The IMPEDE VTE score is used to assess VTE risk in myeloma patients on immunomodulatory drugs (like lenalidomide in many regimens). While this regimen doesn't include an IMiD, her personal risk factors (obesity, prior VTE) place her at high risk. For patients requiring anticoagulation (not just antiplatelet therapy), direct oral anticoagulants (DOACs) are preferred over warfarin for VTE prophylaxis and treatment. For prophylactic dosing, apixaban 2.5 mg twice daily (or rivaroxaban 10 mg daily) is standard. Option C (rivaroxaban 20 mg) is a treatment dose for an existing clot, not a prophylaxis dose. Aspirin (B) is insufficient for her high-risk profile. Warfarin (D) is less ideal than DOACs due to need for monitoring and drug interactions.

AS presents to the ED and reports that her left lower leg is painful, swollen and warm; she thought she pulled a muscle, but she can’t stretch it out. Symptoms are concerning for VTE.

What are AS’s risk factors for deep vein thrombosis (DVT)?

Answer A. Therapy with lenalidomide and dexamethasone

  • Correct answer is A. Therapy with lenalidomide and dexamethasone increases the risk of blood clots.
  • Answer B is incorrect as bisphosphonate administration is not a risk factor for VTE.
  • Answer C is incorrect as carfilzomib by itself does not increase the risk of blood clots.
  • Answer D is incorrect as normal weight is not considered a risk factor; however, obesity is a risk factor

SB is a 62-year-old female with newly diagnosed low risk smoldering myeloma with a serum monoclonal protein of 3.5 g/dL and 15% plasma cells in the bone marrow. Her baseline labs include SCr 0.60 mg/dL, calcium 9.2 mg/dL, Hgb 12.7 g/dL. According to the NCCN Clinical Practice Guidelines in Oncology, which of the following would be the most appropriate therapy for SB?

Correct answer is A (observation). Smoldering myeloma requires observation as it is a plasma cell proliferative disorder with a risk of progressing into active MM; however, chemotherapy is reserved for the management of patients with active MM.

Answers B, C, and D are all treatment regimens reserved for patients with active MM and are not appropriate for a patient with smoldering myeloma.

TL is a 62-year-old male with newly diagnosed multiple myeloma. His corrected calcium is 11.8 mg/dL, 55% plasma cells on bone marrow pathology, R-ISS stage III (β2M of 7.5 mg/L; high risk cytogenetics including t(14;16)), and SCr 0.91. ECOG status 0. He is eligible for autologous stem cell transplant and will be starting primary induction therapy.

TL is a 62-year-old male with newly diagnosed multiple myeloma. His corrected calcium is 11.8 mg/dL, 55% plasma cells on bone marrow pathology, R-ISS stage II (β2M of 7.5 mg/L; intermediate-risk cytogenetics including t(11;14)), and SCr 0.91. ECOG status 0. He is eligible for autologous stem cell transplant and will be starting primary induction therapy.

Which of the following is the most appropriate first-line treatment option for TL according to the NCCN Guidelines?

Correct answer is D (Bortezomib, lenalidomide, dexamethasone).

TL is a guitarist and concerned about developing peripheral neuropathy (PN) from his treatment. Following a discussion of potential options for induction therapy, TL inquires which of following bortezomib-based regimens is least likely to cause PN?

  • A. 1.3 mg/m2 SubQ days 1, 4, 8, 11
  • B. 1.3 mg/m2 IV days 1, 8, 15, 22
  • C. 1.3 mg/m2 IV days 1, 4, 8, 11
  • D. 1.5 mg/m2 IV days 1, 8, 15, 22

Correct answer is A (1.3 mg/m2 SubQ days 1, 4, 8, 11). SubQ administration of bortezomib has exhibited reduced all-grade peripheral neuropathy when compared to IV bortezomib.

Answers B, C, and D are all administered intravenously, which has exhibited increased peripheral neuropathy when compared to SubQ administration. Patients who received weekly bortezomib vs administration on days 1,4, 8, and 11 experienced similar incidence of peripheral neuropathy; however, the total bortezomib dose per cycle was higher in the weekly group and they required fewer dose reductions.

TL was treated with 4 cycles of induction VRd (bortezomib, lenalidomide, dexamethasone), ASCT, and 2 cycles of VRd consolidation and achieved a complete response. He then continued lenalidomide maintenance until presenting 4 years later with progressive disease, now requiring further therapy. Which of the following is the most appropriate therapy for TL at this time according to the NCCN Guidelines?

Following 4 cycles of induction VRd, ASCT, and 2 cycles of VRd consolidation, TL then continued maintenance therapy with lenalidomide until presenting 4 years later with progressive disease, now requiring further therapy. The patient has still maintained a good performance status and organ function. Which of the following is the most appropriate therapy for TL at this time according to the NCCN Guidelines®?

Correct Answer is C (Isatuximab, carfilzomib, dexamethasone).

  • Isatuximab, carfilzomib, dexamethasone is a category 1 recommendation from the NCCN Guidelines for relapsed multiple myeloma with early relapse.
  • Answer A, B, and C are all therapies recommended to be used in late relapse (>3 prior lines of therapy) by the NCCN Guidelines and there are other treatment options that would be more preferred and appropriate for TL at this time.

TL is treated with isatuximab, carfilzomib, and dexamethasone for 1 year, and then progresses. He is then treated with third line elotuzumab, pomalidomide, dexamethasone and then also fourth line selinexor, bortezomib, dexamethasone. He presents to your clinic with a rising free light chain ratio, increase in his M-spike, and a new osteolytic lesion, all indicative of disease relapse. TL is to start fifth line treatment with teclistamab. The patient mentions his concern for the cytokine release syndrome with teclistamab that he had read on an online myeloma patient forum.

Which of the following is the most appropriate premedication regimen to recommend upon initiation of teclistamab to reduce the risk of cytokine release syndrome?

Correct Answer is B (Dexamethasone, acetaminophen, diphenhydramine).

  • Patients receiving teclistamab should receive dexamethasone, an antipyretic (i.e. acetaminophen), and a histamine-1 receptor antagonist (i.e. diphenhydramine) prior to at least the 0.06 mg/kg, 0.3 mg/kg, and 1.5 mg/kg step-up doses when initiating teclistamab in order to reduce the risk of cytokine release syndrome.
  • Answer A is incorrect as patients should also receive diphenhydramine (or equivalent histamine-1 receptor antagonist) prior to teclistamab initiation along with dexamethasone and acetaminophen.
  • Answer C is incorrect as dexamethasone is missing from the premedication regimen and should be administered along with acetaminophen and diphenhydramine.
  • Answer D is incorrect as the premedication regimen is missing dexamethasone and also because tocilizumab is not a recommended premedication to be given prior to teclistamab.
[su_not]

TL is treated with isatuximab, carfilzomib, and dexamethasone for 1 year, and then progresses. He is then treated with third line selinexor, bortezomib, dexamethasone and then also fourth line elotuzumab, pomalidomide, dexamethasone. He presents to your clinic with a new osteolytic lesion with a pathologic fracture, rising free light chain ratio, and an increase in his M-spike, all indicative of disease relapse. His complete blood count is within normal limits. TL is to start fifth line treatment with teclistamab.

Which of the following is the most appropriate antimicrobial prophylaxis to recommend upon initiation of teclistamab?

Correct Answer is A (Acyclovir).

  • Patients receiving teclistamab should receive at least herpes zoster reactivation prophylaxis during therapy, with an agent such as acyclovir, famciclovir, or valacyclovir.
  • Answer B is incorrect as there are no current recommendations for providing cytomegalovirus prophylaxis for patients receiving teclistamab.
  • Answer C is incorrect as antibacterial prophylaxis with levofloxacin is not warranted in this setting, as the patient is not neutropenic with having a CBC within normal limits, and is not otherwise recommended as empiric prophylaxis with teclistamab.
  • Answer D is incorrect as it omits acyclovir, which is needed prophylaxis in this setting.
[/su_note]

TL completes 4 cycles of induction with VRd, then proceeds to an autologous stem cell transplant, followed by 2 cycles of VRd consolidation. He achieves a complete response and is now to be considered for maintenance therapy. According to the NCCN Guidelines, which of the following would be the most appropriate maintenance therapy for TL?

Correct answer is B (Lenalidomide)

  • Lenalidomide is a category 1 recommended maintenance therapy for patients after undergoing ASCT. It has demonstrated an improvement in overall survival.
  • Answer A is incorrect, as bortezomib is not over lenalidomide in the maintenance setting as it has not demonstrated an improvement in overall survival, however, can be an option for patients as an alternative to lenalidomide.
  • Answer C is incorrect as the patient does not have high-risk cytogenetics; doublet maintenance would otherwise be recommended in the setting of high-risk MM.
  • Answer D is incorrect as maintenance therapy is recommended regardless of the depth of response obtained following ASCT in MM.

With his most recent relapse of his myeloma, TL also has an osteolytic lesion. His oncologist would like to resume a bone modifying therapy at this time. His CrCl is 70 mL/min. Which of the following is the most appropriate to recommend for TL at this time?

Correct answer is C (Denosumab 120 mg SubQ every 4 weeks).

With his most recent relapse of his myeloma, TL also has a new osteolytic lesion of the right femur. His oncologist would like to resume a bone modifying agent. His CrCl is 35 mL/min. Which of the following is the most appropriate to recommend for TL at this time?

Correct answer is D (Zoledronic acid 3 mg IV over 15 mins every 4 weeks).

  • As per the NCCN Guidelines, all patients with active multiple myeloma, regardless of presence of lytic bone lesions, should receive bone modifying therapy with a bisphosphonate or denosumab. Zoledronic acid, denosumab, and pamidronate are all recommended options as per both the ASCO and NCCN Guidelines.
  • Answer A is incorrect as it is the incorrect route of administration for denosumab; it is to be administered as a subcutaneous injection, not an IV infusion.
  • Answer B is incorrect as the 60 mg dose is the FDA approved dose for denosumab as marked as Prolia® for osteoporosis.
  • For Answer C, although the route of administration and frequency of administration is correct, the answer is incorrect as the dose of zoledronic acid needs to be adjusted in the setting of renal dysfunction, as the patient has a CrCl of 35 mL/min. The dose of zoledronic acid needs to be adjusted to 3 mg, and therefore D is the correct answer.

NK is a 63-year-old male who presents to the emergency department with significant confusion and lethargy. He also reports not having a bowel movement for several days. His labs are notable for a serum calcium of 15.6 mg/dL, SCr 3.1 mg/dL, and albumin of 3.4 g/dL. Along with aggressive intravenous hydration, which of the following initial interventions would be the most appropriate for NK?

  • A. Zoledronic acid 4 mg IV once + calcitonin 4 IU/kg SubQ every 12 hours
  • B. Zoledronic acid 3 mg IV once + calcitonin 4 IU/kg SubQ every 12 hours
  • C. Calcitonin 4 IU/kg SubQ every 12 hours only, a bisphosphonate is contraindicated with his renal function
  • D. Denosumab 120 mg IV once

Correct answer is A (Zoledronic acid 4 mg IV + calcitonin 4 IU/kg SubQ).

NK receives appropriate treatment for his hypercalcemia of malignancy, undergoes a bone marrow biopsy, and is stabilized and discharged home with a follow visit in your clinic. His bone marrow biopsy reveals 50% involvement by plasma cells and he is ultimately diagnosed with IgG kappa multiple myeloma. He is to start induction therapy with bortezomib, lenalidomide, and dexamethasone. While counseling the patient on his new regimen, you also assess his risk of venous thromboembolism (VTE). He is African American, no recent history of surgery, no history of VTE, and will receive 120 mg of dexamethasone per cycle. You calculate his SAVED score to be 1. According to the SAVED criteria, which of the following is most appropriate for NK?

  • A. Aspirin 81 mg once daily
  • B. Apixaban 2.5 mg twice daily
  • C. Enoxaparin 40 mg once daily
  • D. No thromboprophylaxis required

Correct answer is A (Aspirin 81 mg once daily).

  • NK is deemed to be at a low risk of VTE based on the SAVED scoring system, as therefore aspirin 81 mg once daily would be appropriate.
  • Answer B and C are incorrect due to the patient having a SAVED score <2. If his SAVED score was >2 and he was considered high risk for VTE, then either of these would be appropriate options. Answer D is incorrect as thromboprophylaxis is indicated in this patient who is to receive an immunomodulatory drug (lenalidomide) and dexamethasone.

Upon presenting to the clinic for Cycle 2 Day 1 of bortezomib, lenalidomide, and dexamethasone, NK reports lower extremity swelling in his right leg. Ultrasound doppler reveals a deep vein thrombosis (DVT) despite NK having taken adequate thromboprophylaxis. Pertinent labs and findings: 63 kg, SCr 1.1 mg/dL, platelets 130,000/mm3. According to the NCCN Guidelines, which of the following is the most appropriate treatment of NK’s DVT?

Correct answer is D (Enoxaparin 60 mg SubQ q12hr).

  • Enoxaparin 1 mg/kg every 12 hours is the most appropriate agent to initiate at this time.
  • Option A is incorrect because edoxaban when used treatment for an acute DVT in the setting of cancer should be first preceded by at least 5 days of parenteral anticoagulation.
  • Option B is incorrect because rivaroxaban must be first administered as a loading dose of 15 mg twice daily for 21 days before continuing on the 20 mg once daily maintenance dose.
  • Option C is not appropriate at this time because the patient is not thrombocytopenic (platelets are >50,000/mm3). Adjusting the dose of LMWH to 0.5 mg/kg every 12 hours would be appropriate in the setting of platelets being 25,000-50,000/mm3; however, with the patient’s platelets being 130,000/mm3, this would be underdosing the patient.

AM is a 76-year-old male with a past medical history significant for type 2 diabetes, peripheral neuropathy, and hypertension now found to have newly diagnosed high-risk smoldering myeloma with a serum monoclonal protein of 4.2 g/dL and 20% plasma cells in the bone marrow. His baseline labs include Hgb 12.5 g/dL, SCr 0.80 mg/dL, corrected calcium 9.4 mg/dL. According to the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines), which of the following would be the most appropriate therapy for AM?

Correct answer is D (observation).

Smoldering myeloma requires observation as it is a plasma cell proliferative disorder with a risk of progressing into active MM; however, induction therapy is reserved for the management of patients with active MM. Clinical trial where available is also a recommended consideration for patients with high-risk smoldering myeloma.

Answers A, B, and B are all treatment regimens reserved for patients with active MM and are not appropriate for a patient with smoldering myeloma.

KN is 50 years old man ,he was diagnosed by ISS stage III MM his medical history is significant for CHF ,he has completed 4 cycles of VRd (bortezomib, lenalidomide, dexamethasone after his 4th cycle he presented with symptoms suggesting a progressive disease that was confirmed by work up, now requiring further therapy. Which of the following is the most appropriate therapy for KN at this time?

Answer: C. Daratumumab, carfilzomib, dexamethasone (DKd)

Explanation: This patient has progressive disease during initial VRd therapy, meaning his disease is refractory to both bortezomib and lenalidomide. Therefore, options that contain these drugs (A, B, and D) should be avoided. His history of congestive heart failure (CHF) is a critical factor. Carfilzomib has a known risk of cardiovascular events, including heart failure. However, in this scenario of early, aggressive relapse refractory to standard agents, its use may still be necessary but must be managed carefully. The best among the listed options is still DKd (C), as it offers two new, highly effective agents. The clinical team would need to carefully monitor and optimize his CHF treatment. Panobinostat (option A) is a histone deacetylase inhibitor also associated with significant toxicity and is rarely used today.

Which of the following drugs are considered REMS drugs(choose 3)?

Answer: C. Isotretinoin, E. Fentanyl patch, (and based on standard REMS lists, the third is likely A. Alemtuzumab, though D. Duvelisib is also often included).

Explanation: REMS (Risk Evaluation and Mitigation Strategy) is a FDA program for drugs with serious safety concerns.

  • C. Isotretinoin: Has a REMS (iPledge program) due to its extreme teratogenicity.
  • E. Fentanyl patch: Has a REMS (TIRF REMS) due to high risk of abuse, addiction, and fatal respiratory depression.
  • A. Alemtuzumab: Has a REMS program due to risks of autoimmunity, infusion reactions, and malignancies.
  • D. Duvelisib: Also has a REMS due to risks of fatal and serious toxicities (infections, diarrhea, inflammation, rash).
  • B. Ondansetron (an antiemetic) and F. Ifosfamide (chemotherapy with toxicities but no specific REMS) are not typically part of REMS programs. The question asks for 3, so the most classic answers are Isotretinoin, Fentanyl, and Alemtuzumab.

Treatment for myeloma patient relapsed 6 months after Auto SCT is:

  • a. Second AutoSCT
  • b. Allogeneic SCT
  • c. Matched unrelated SCT
  • d. Clinical trials

Answer: d. Clinical trials

Treatment options for relapsed multiple myeloma after an autologous HCT include a second autologous HCT, allogeneic HCT as part of a clinical trial, or treatment with salvage chemotherapy regimens. Patients who relapse within the first 12 months have a shorter median overall survival when compared with those who relapse after 12 months. A second autologous HCT is not recommended for patients who relapse within 12 months of the first, since the progression free survival following the second HCT will most likely be even shorter than the benefit seen with the first transplant. These patients are best treated with active agents that they have not received before or have had good responses to in the past as well as clinical trials investigating novel therapies. The agents with novel mechanisms of action useful in myeloma are monoclonal antibodies (anti- CD38 MoAb, such as daratumumab), cell cycle-specific drugs, deacetylase inhibitors, agents acting on the unfolded protein response, signaling transduction pathway inhibitors and kinase inhibitors. Marizomib is an irreversible proteasome inhibitor administered intravenously. Ixazomib is an orally administered reversible proteasome inhibitor currently investigated in phase I studies. Pomalidomide, like lenalidomide, is an immunomodulatory compound with pleiotropic properties shown to be beneficial in treating MM.

2. Side effects from thalidomide include:

  • a. Somnolence
  • b. Peripheral neuropathy
  • c. Thrombosis
  • d. All of the above

Answer: All of the above

  • Thalidomide is a derivative of glutamic acid, an oral agent with antiangiogenic and immunomodulatory properties. Thalidomide is poorly soluble in water and thus no parenteral preparation is available. Cereblon has been identified as a primary target of thalidomide activity,which is also required for its anti-myeloma activity. Thalidomide binds to and inactivates cereblon, which leads to an antiproliferative effect on myeloma cells
  • Thalidomide can cause constipation, weakness, fatigue, or somnolence in about 25% patients. A dose-dependent peripheral neuropathy (sensory more than motor axonal neuropathy) occurs in up to 30–80% of patients with prolonged therapy, and may not be reversible. Thrombotic complications can occur with thalidomide therapy and incidence increases up to 25% of patients when thalidomide plus dexamethasone are used. The severity of sedation appears to decrease with continued administration at a constant dose and can be minimized by taking the drug in the evening before going to bed. Constipation is a common side-effect and its severity may be dose-related. The most serious adverse effects associated with thalidomide are deep vein thrombosis and peripheral neuropathy.

3. True regarding lenolidomide are, all except:

Answer: c. Safe in renal failure

  • Lena­li­do­mi­de is a syn­the­tic com­po­un­ds de­ri­ve­d by modi­fy­ing the che­mi­cal struc­ture of thal­ido­mi­de to im­pro­ve its po­ten­cy and re­duce its side ef­fects. Lena­li­do­mi­de is a 4-amino-glut­amyl analogue of thal­ido­mi­de that lacks the neu­rol­ogic side ef­fects of sed­a­tion and neu­ro­pat­hy. It is ap­pro­ved by FDA for clini­cal use in myel­odys­plas­tic syn­dromes with de­le­tion of chromosome 5q and mul­ti­ple myel­oma. The im­mune sys­tem has two ma­jor com­pon­ents, one is ce­llular (media­ted by ma­cro­phages, den­dr­itic cells, NK-cells, T-cells and B-cells), and the se­cond is hum­oral com­pon­ent (media­ted by an­tib­o­dies, cy­to­kines). Lena­li­do­mi­de is an im­munom­odul­ator, af­fec­ting both ce­llular and hum­oral com­pon­ents of the im­mune sys­tem. It also has anti-angi­ogenic pro­per­ties.
  • The immune system can prevent development of cancers by multiple ways including suppressing oncogenic agents, altering the local milieu conducive to tumor growth, and by immune surveillance by identifying and destroying cancer cells. Lena­lidomide has been shown to inhibit production of pro-inflammatory cytokines TNF-a, IL-1, IL-6, IL-12 and elevate the production of anti-inflammatory cytokine IL-10. Reduction in IL-6 and TNF-a levels leads to its antimyeloma activity. IL-6 inhibits the apoptosis of myeloma cells and helps in their proliferation. Lena­lidomide downregulates the production of IL-6 and thus effective in myeloma.
  • The most common severe (grade 3/4) toxicities seen in patients treated with lena­lidomide plus dexamethasone include neutropenia (30 to 40%), anemia (9 to 13%), thrombocytopenia (12 to 15%), and venous thromboembolism (11%).
  • Lenalidomide is secreted via the kidneys and should be used with caution in patients with renal impairment. For multiple myeloma patients, the normal starting dose of lenalidomide is 25 mg/day on days 1 to 21 of repeated 28-day cycles. According to new recommendations, patients with moderate kidney impairment should only receive 10 mg/day, and patients with severe kidney impairment should only receive 15 mg every other day.
  • Prolonged treatment can lead to difficulty in harvesting stem cells. With the prolonged use of lenalidomide -1) the number of CD34+ cells collected is reduced, 2) the number of collections to obtain a target number of cells increased, and 3) the number of failed collections is increased in patients whose initial therapy contained lenalidomide when mobilized with G-CSF alone. However, upto four cycles of lenalidomide exposure have minimal negative impact on PBSC collection.
  • Other reported long-term complications with the use of lenalidomide are risk of second malignancies. Tumor flare reaction has also occurred during the use of lenalidomide for CLL and lymphoma, and is characterized by tender lymph node swelling, low grade fever, pain and rash

4. Side effects of bortezomib are, all except:

  • a. Peripheral neuropathy
  • b. Thrombosis
  • c. Cutaneous reactions
  • d. Increased risk of herpes zoster

Answer: b. Thrombosis

  • Bortezomib is a novel proteasome inhibitor. It functions in myeloma via the inhibition of the breakdown of inhibitory kappa B (IkB) and consequently stabilization of the nuclear factor kappa B (NFkB) complex.
  • This prevents NFkB translocation to the nucleus with consequent inactivation of multiple downstream pathways known to be important in myeloma cell signaling. Other effects in myeloma include inhibition of angiogenesis, inhibition of DNA repair and impairment of osteoclast activity. Peripheral neuropathy is the most common dose limiting toxicity. Peripheral neuropathy, often painful, develops in approximately 35 percent of patients. It is more frequent and severe in those who have previously received neurotoxic therapy and those with preexisting neuropathy.
  • Thrombocytopenia occurs in 43 percent of patients but is rarely severe enough to postpone subsequent cycles. Platelet count nadir typically occurs at day 11 and drops to approximately 40 percent of baseline. Bortezomib therapy may be associated with an increased risk of herpes zoster (varicella zoster reactivation). Antiviral prophylaxis should be given to all patients receiving bortezomib therapy with acyclovir 400 mg twice daily or valacyclovir 500 mg once daily. Lenaildomide and thalidomide along with steroids cause thrombosis and should be given aspirin prophylaxis

ZP is a 69-year-old female with a history of congestive heart failure who presents to your clinic. She was recently diagnosed with symptomatic stage Ill
multiple myeloma. Which of the following chemotherapy regimens would be most appropriate for her?

Answer D

  • Considering the patient has a history of congestive heart failure and her age is greater than 65, ZP is not an ideal candidate for autologous hematopoietic stem cell transplant (HSCT). Per the NCCN guidelines, bortezomib/Lenalidomide/dexamethasone is considered a preferred option for newly diagnosed multiple myeloma patients regardless of autologous HSCT status. Thus, the last answer would be the most appropriate option.
  • Any regimen that increases the risk of cardiotoxicity should be avoided first and third answers!
  • Dexamethasone alone (second answer) has lower response rates and would be an inferior regimen. Compared to dexamethasone alone, lenalidomide/dexamethasone led to higher overall response, longer time to progression, and progression-free survival (PFS). Furthermore, studies have shown statistically significant improvement in PFS and overall survival (OS) with bortezomib/Lenalidomide/dexamethasone vs. lenalidomide/dexamethasone.

KM is a 73-year-old male who was identified as having elevated protein on a routine exam. Further work-up through serum protein electrophoresis.
revealed elevated monoclonal protein. Which of the following tests would be appropriate for diagnostic and staging work-up for multiple myeloma?

  • A. Chest X-ray, bone marrow biopsy, skeletal survey 6%)
  • B Chest X-ray. skeletal survey. B2 microglobulin (5%)
  • C Bone marrow biopsy. skeletal survey, B2 microglobulin (83%).
  • D Bone marrow biopsy. B2 microglobulin, chest X-ray (7%)

Answer C

  • Per the NCCN guidelines, the initial diagnostic workup for multiple myeloma includes CBC and differential, serum BUN/creatinine, electrolytes, albumin and calcium, serum LDH and β2 microglobulin, serum quantitative immunoglobulins, serum protein electrophoresis (SPEP), serum immunofixation electrophoresis (SIFE), serum free light chain assay, skeletal survey or whole body PET/CT scan, and bone marrow biopsy.
  • Thus, the third answer is correct. A bone marrow biopsy with at least 10% of plasma cells with other tests is needed to confirm the diagnosis of multiple myeloma. Multiple myeloma likes to metastasize to the bone; therefore the skeletal survey will help rule out bone metastasis and further diagnosis of multiple myeloma. β2 microglobulin has prognostic value and is essential for staging patients based on the Revised Multiple Myeloma International Staging System (R-ISS).
  • A chest x-ray does not help in the diagnostic or staging work-up for multiple myeloma (first, second and last answers).

JJ is a 74-year-old female who was recently diagnosed with multiple myeloma. Which of the following is the most appropriate answer?

Multiple myeloma is a disorder of

Answer A

  • The first answer is correct as multiple myeloma is a disorder of abnormal overproduction of plasma cells. This results in increased production of abnormal antibodies made of protein.
  • Macrophages (second answer) are not involved in the pathophysiology of multiple myeloma.
  • At times, a patient may have low level of platelets due to plasma cells overtaking the bone marrow and affecting the production of other cell lineages. Thus, the third answer is incorrect.
  • Plasma cells are derived from B-lymphocytes and not T-lymphocytes (last answer).

Multiple myeloma is a hematologic malignancy primarily affecting the older population and may target multiple organ systems.

Which of the following Clinical manifestations are associated with multiple myeloma?

Answer: B

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