Adhoc Assistant Professor Tata Memorial Hospital Mumbai, Maharashtra, India
Introduction: Multiple Myeloma (MM) is a heterogeneous disease with a genetic profile playing a major role in prognosis and treatment outcome. The high risk genetic abnormalities defined by mSMART 3.0 are t(4;14), t(14;16), t(14;20), del 17p, p53 mutation and gain 1q. Ultra High-Risk Myeloma includes double-hit MM (coexistence of two high-risk abnormalities) and triple-hit MM (coexistence of three high-risk abnormalities). Ultra High-Risk subset is associated with poor prognosis and real-world data on management are limited.
Methods: The hospital OPD registry of newly diagnosed Multiple Myeloma patients registered between January 2016 and December 2019 was searched to find 48 patients with ultra-high-risk Myeloma. We retrospectively analyzed the demographics, management, and outcome of ultra-high-risk patients. SPSS descriptive statistics were performed for demographic characteristics. Kaplan-Meier plots were used for survival analysis. Univariate analysis was done to see the impact of baseline characteristics on progression-free survival (PFS) and overall survival (OS).
Results: The median age of the population was 54.5 years (range 28 years – 72 years). Thirty-one patients (64.6%) were Male. ECOG PS was 0-2 in 35 patients (72.9%). Thirty-two patients (66.7%) had ISS III and R-ISS III disease. 23 (47.9%) received Proteosome Inhibitor (PI)-based triplet (VCD/VMP) and 22 (45.8%) received PI+Immunomodulatory agents (IMiD) based triplet (VRD/VTD/VPD) as initial therapy. The median PFS was 20 months (95% CI: 0 – 42.63), the median second progression free survival (PFS2) was 1 month (95% CI not calculable) and the median OS was 25 months (95% CI: 9.48 – 40.52). On univariate analysis, PFS and OS were not associated with baseline co-morbidities, ECOG PS, ISS, R-ISS, or the presence of plasma cells in peripheral blood. The presence or absence of del 17p or p53 mutation also did not affect survival outcomes. Similarly, the presence of double-hit versus triple-hit did not affect the PFS or OS of the patients and autologous hematopoietic stem cell transplant (auto-HSCT) was not associated with significantly improved PFS and OS in our analysis. Only 5 patients underwent auto-HSCT post-induction chemotherapy. Patients who received maintenance had a significantly better median PFS (44 months vs 8 months) and median OS (68 months vs 9 months). The magnitude of benefit from different maintenance strategies cannot be ascertained due to the small number.
Conclusions: Our analysis gives us a real-world experience of the ultra-high-risk subgroup and adverse outcomes similar to other studies reported in this group of patients. Our study did show improved outcomes with maintenance in this subgroup of patients. Large-scale prospective data is required to understand the outcomes and best management strategies for this adverse risk group of Multiple Myeloma patients.
