Comparison of Melphalan 200 mg/m2 versus Melphalan 140 mg/m2 as Conditioning regimen in Newly Diagnosed Multiple Myeloma.

Multiple Myeloma (MM) is a common blood cancer affects which accounts for 1.2% of cancers in India. The standard treatment for newly diagnosed patients with myeloma who can receive a transplant includes a combination of multiple medicines like Bortezomib, Lenalidomide, and Dexamethasone (VRd) with/without Daratumumab followed by stem-cell transplant and Lenalidomide maintenance.Transplant is a process which is commonly done after few cycles of chemotherapy when the cancer comes under control. For transplant, high doses of a chemotherapy medicine called melphalan is used. The standard dose of melphalan used for transplant is 200 mg/m², but a lower dose of 140 mg/m² is used for patients who are perceived to be at higher risk of complications. In today’s era, for assessing how much a cancer has come under control – a special test called minimal residual disease (MRD) is used. MRD means the least amount of cancer cells which are present in a patient’s body. It is known that in myeloma, patients who become MRD negative for their cancer have a better outcome in long run in contrast to others. This concept is similar to other blood cancers (like acute lymphoblastic leukemia) wherein MRD carries a lot of significance. The standard dose of melphalan was established two decades back when special tests like MRD were not available. In our practice, we have been doing MRD prior to transplant in all our myeloma patients who undergo transplant. Melphalan doses are reduced depending on patient’s clinical condition and organ functions prior to transplant. There is limited data comparing the outcomes of standard versus lower doses of melphalan, especially in today’s MRD era. We will address the above question in this prospective randomised study.

   We recently analysed our 15-year data of transplants and showed that lower dose of melphalan i.e., Mel-140 may be as equally effective as Mel-200 in people who respond well to initial treatment. Importantly, Mel-140, as compared to Mel-200 also has less side effects. In low-income nations like India, Mel-200 frequently commonly results in more severe side effects like severe mouth sores, deadly infections, and extended hospital admissions. A significant question which was brought up by our above study is that if Mel-200 is still the standard dose for all patients in the modern era of treatment? This study will test whether Mel-140 is just as effective as Mel-200 in patients who have already responded well to initial treatment (achieving what’s called a "very good partial response" or better). It will look at how many patients have no remaining signs of cancer (called MRD negativity) 100 days after transplant. MRD testing is commonly done from bone marrow in myeloma. Bone marrow is the factory in our body wherein commonly all healthy blood (including cells implicated in myeloma – called plasma cells) are made. Bone marrow testing means taking out a small amount of liquid from the hip bone for testing. Our study will compare MRD testing modality from bone marrow (which is the current accepted standard), and compare it with MRD test with other modalities (like a scan of the whole body called PET-CT). If this trial is successful, it may demonstrate that a lesser dose of chemotherapy is safer and effective for transplant in myeloma. Consequently, this would make transplantation less risky and easier, particularly for patients in low and middle-income nations like India