Medicine · Hematological Malignancies (Leukemias, Lymphoma, Myeloma, Myeloproliferative)

A 72-year-old man presents with bone pain, serum calcium 12.4 mg/dL, total protein 10.2 g/dL, IgG kappa M-protein 4.2 g/dL on SPEP, and 38% plasma cells on bone marrow biopsy. FISH shows t(4;14). Which of the following is the MOST appropriate initial treatment for this transplant-ineligible patient?

  • A Melphalan + prednisone (MP)
  • B Bortezomib + melphalan + prednisone (VMP)
  • C Daratumumab + lenalidomide + dexamethasone (DRd)
  • D Thalidomide + dexamethasone
Correct answer: C. Daratumumab + lenalidomide + dexamethasone (DRd)

Explanation

This patient has symptomatic multiple myeloma (CRAB criteria: hypercalcaemia, bone lesions). For transplant-ineligible patients, the MAIA trial (NEJM 2019) showed daratumumab + lenalidomide + dexamethasone (DRd) significantly improved PFS and OS vs. Rd alone; DRd is now a preferred first-line regimen per IMWG 2022 guidelines. t(4;14) is an adverse cytogenetic marker but does not preclude this regimen. VMP is an alternative (ALCYONE trial) but DRd is preferred. MP without novel agents is obsolete. Daratumumab, an anti-CD38 monoclonal antibody, provides substantial depth of response.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.

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