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Question 1

Patient history: Helen, a 68-year-old architect, was newly diagnosed with multiple myeloma 4 months ago, after presenting with fatigue and recurrent infections. A bone marrow biopsy showed 65% plasma cells. Magnetic resonance imaging did not reveal focal lesions at the initial diagnosis. Her disease was classified as ISS stage II.

Initial laboratory results showed an IgG-type serum M protein level of 4.0 g/dL and a serum albumin level of 3.0 g/dL. Hematology tests indicated anemia (Hb: 9.5 g/dL). The patient’s renal function was not significantly impaired (serum Cr: 0.8 mg/dL; CrCl: 80 mL/min). No major cytogenetic abnormalities were detected on fluorescence in situ hybridization analysis.

  • Treatment regimen and response: Helen was cleared for autologous stem cell transplantation (ASCT) by her cardiologist. Induction therapy consisted of daratumumab plus bortezomib, lenalidomide, and dexamethasone (D-VRd), administered in standard doses. Helen achieved partial response (PR) after continuing the D-VRd regimen for 4 cycles. After the second D-VRd cycle, she acquired a respiratory infection, which resolved after treatment with levofloxacin.
  • Comorbidities: atrial fibrillation, well-controlled hypertension, and mild asthma.

  • Current presentation: Helen remains moderately active at work and at home, with an ECOG performance status score of 1. Her asthma symptoms have improved and the hypertension remains well controlled with medication.

    Current laboratory results show a 50% reduction in serum M-protein levels. Serum creatinine, calcium, and lactate dehydrogenase levels are within the normal ranges. Serum albumin levels have increased to 3.5 g /dL. Hematology tests continue to indicate anemia (Hb: 9.0 g/dL).

  • Challenge: Response to the induction therapy is partial after 4 cycles. Helen states that she has been experiencing fatigue and weakness on some days but that she feels well overall.

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References:

1. Kumar L, Hussain MM, Chethan R, Sahoo RK, Malik PS, Sharma OD, et al; for AIIMS Myeloma Group. Multiple Myeloma: Impact of Time to Transplant on the Outcome. Clin Lymphoma Myeloma Leuk 2022; 22(9):e826-e835.

2. Richardson PG, Jacobus SJ, Weller EA, Hassoun H, Lonial S, Raje NS, et al; DETERMINATION Investigators. Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma. N Engl J Med 2022; 387(2):132-147.

3. Moreau P, Hulin C, Perrot A, Arnulf B, Belhadj K, Benboubker L, et al. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol 2021; 22(10):1378-1390.

4. Sonneveld P, Dimopoulos MA, Boccadoro M, Quach H, Ho PJ, Beksac M, et al; PERSEUS Trial Investigators. Daratumumab, Bortezomib, Lenalidomide, and Dexamethasone for Multiple Myeloma. N Engl J Med 2024; 390(4):301-313.

5. Medina-Herrera A, Sarasquete ME, Jiménez C, Puig N, García-Sanz R. Minimal Residual Disease in Multiple Myeloma: Past, Present, and Future. Cancers (Basel) 2023; 15(14):3687.

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