MINIMAL RESIDUAL DISEASE ASSESSMENT IN MULTIPLE MYELOMA: UTILITY AND FEASIBILITY IN RESOURCE CONSTRAINT SETTINGS OF INDIA

Abstract

Introduction: Financial means of a patient is major factor influencing management of multiple myeloma (MM) in India. Outside of clinical trials, physicians have to settle for varying drug combinations with/without autologous stem cell transplant (ASCT). The cost of treating MM with ASCT at our institute is around USD 3000. The financial burden mostly falls on the patient, as public/private medical insurances are available only to minority. Most state-funded tertiary care hospitals can provide serum protein electrophoresis (SPE), immunofixation electrophoresis (IFX), and morphological assessment of bone marrow (BM) plasma cell (PC) percentages. We introduced minimal residual disease (MRD) assessment by multicolour flow cytometry (MFC) at subsidized cost and analyzed its utility and feasibility. Method(s): A total of 52 newly diagnosedMMpatients were included in the study. Upfront therapy included lenalidomide or thalidomide or cyclophosphamide in combination with Bortezomib and dexamethasone. Financial constraints in majority made ASCT possible only in 16 patients. MRD assessment on BM aspirate was done at end-induction or day +100 post-transplant. Six-colour flow cytometry was used for MRD assessment with pre-titrated cocktails of CD38, CD138, CD19, CD45, cytoplasmic kappa and lambda light chains, CD56, CD81, CD27, CD28, and CD200 in combinations of 3 tubes. At least 1 million events were acquired in each tube, and MRD positivity was reported at a sensitivity of 0.01%. This test was offered at a cost of USD 37 (INR 2500). Result(s): There were 32 men and 20 women with mean age of 53.4 years. MFC identified 22 (42%) individuals with residual clonal PCs (range = 0.01 to 6.44%), including 3 in ASCT group. Positive IFX was noted in 12 and M-band in 8 out of 22 MRD-positive patients. BM morphology revealed >5% PCs in 4 out of 22 MRD-positive patients. PC percentage on morphology was significantly higher in MRD-positive group (p = 0.05), whereas the leukocyte counts were lower (p = 0.005). However, no significant difference was noted between the MRD status and age and sex distribution, mean values of hemoglobin, platelet count, serum creatinine, serum calcium and serum albumin. Mean follow up of around 13 months did not reveal a statistical difference in overall and progression-free survival between MRD-positive and negative groups. Conclusion(s): MRD by MFC is sensitive technique and should be feasible at a relatively low cost (<50 USD) in most state-funded hospitals in India. In our hands, it had a better sensitivity than SPE and IFX in assessing residual disease, and we propose its routine incorporation in monitoring of MM. Although, we could not demonstrate difference in overall and progression-free survival based on MRD status, it is understandable that a longer follow up and upgradation to 8 to 10 colour flow with increased sensitivity of MRD detection would be able to show more realistic outcomes.