Is Less “Sufficient” and “Safe” in the MRD Era - Outcomes of Autologous Stem-Cell Transplant as per Melphalan Dose in Patients with Multiple Myeloma

Multiple Myeloma (MM), with an incidence of 1 per 100,000, accounts for 1.2% of all cancers in India [ 1 ]. Bortezomib-Lenalidomide-Dexamethasone (VRd) with or without Daratumumab, followed by autologous stem-cell transplant (ASCT) and lenalidomide maintenance is the standard-of-care (SOC) treatment for newly diagnosed transplant-eligible MM [ 2 ]. While melphalan 200 mg/m 2 is the standard conditioning, a lower dose of 140 mg/m 2 is used in patients perceived to be at risk of excess toxicity. The only randomized trial which compared Melphalan 200 mg/m 2 versus 140 mg/m 2 used an additional 8 gray total-body-irradiation in the Melphalan 140 mg/m 2 arm. It showed that the median survival was higher, with lesser toxicities in Melphalan 200 mg/m 2 arm, consequent to which it became the SOC [ 3 ]. Over last two decades, Melphalan 200 mg/m 2 has been compared with other intensive chemotherapy or radiation-based conditioning regimens. All of these showed lesser toxicity with equivalent survival for Melphalan 200 mg/m2. Hence, it still remains the undisputed standard after nearly 25 years [ 4 ]. Previous retrospective analyses of Melphalan 200 mg/m 2 versus 140 mg/m 2 , including studies from EBMT [ 5 ], MDACC [ 6 ] and India [ 7 ], have shown similar survival for lower-dose of melphalan, especially in patients with ≥VGPR pre-ASCT. Additionally, while transplant-related mortality (TRM) remains