Background

Despite recent advances in the treatment of Multiple Myeloma (MM), triple-class refractory patients—those refractory to proteasome inhibitor (PI), immunomodulatory drug (IMiD), and anti-CD38 antibody—have a poor outcome. We describe a triple refractory t(11,14) Multiple Myeloma (MM) who achieved Very Good Partial Response (VGPR) with Low dose Venetoclax (200 mg) based triplet therapy and underwent successful Autologous stem cell transplantation (ASCT) and remaining in remission till date.

Case discussion

46-year-old male diagnosed as IgG Lambda MM, FISH t(11:14) and was started on Bortezomib + Cyclophosphamide + Dexamethasone chemotherapy. Since he was refractory, Daratumumab + Carfilzomib + Pomalidomide + Dexamethasone - 4 cycles were given on which he achieved near 50% reduction in M protein, with bone marrow showing 27% immature monoclonal plasma cells. He was then started on Venetoclax (200mg daily – from days 1-28) + Carfilzomib (56 mg/m2) + Dexamethasone (40 mg) - on days 1, 8, and 15, with no antifungal prophylaxis. After 3 cycles, he achieved VGPR. Bone marrow study came normal with negative minimal residual disease. He was taken up for ASCT with High dose Melphalan. At 100 days post-transplant he continues to be in VGPR. Maintenance Venetoclax (100mg) with Carfilzomib every other week was started. No drug-related adverse event has been reported so far other than grade 1 neutropenia. At present, 10 months post-transplant, he is still maintaining VGPR. He has no disease-related symptoms and describes a good quality of life.

Conclusion

Our case showcases very low dose of VEN (100-200 mg) in combination with Carfilzomib and Dexamethasone for triple refractory MM. Such dosing is worth further exploring especially in a country like India, because of cost effectiveness and having a very favourable safety profile. VEN represents a unique targeted approach and large-scale prospective studies are further required to validate utility of Low dose Venetoclax based triplet regimens in translocation t(11;14) MM.