Outcomes of patients with primary refractory multiple myeloma in the era of triplet and quadruplet induction therapy.

Patients with multiple myeloma (MM) that do not respond to initial therapy have worse outcomes compared to primary responders, and effective treatments are lacking in this population. However, the outcomes of primary refractory disease in the modern treatment era have not been studied. We reviewed MM patients treated with triplet/quadruplet therapy in our institution to assess the incidence of primary refractory disease and the impact of salvage therapies in this population. We identified 1127 patients, of which 1086 were evaluated for hematologic response after 4-6 cycles. Of these, 93.3% (1013) had evidence of response, while 6.7% (73) had primary refractory disease. With a median OS of 51.3 months, patients with primary refractory disease had an increased risk for shorter survival in univariable and multivariable analysis (HR= 3.5, 95%CI= 2.5 - 4.9, HR= 4.3, 95%CI= 2.6 - 6.9, respectively). In subgroup analysis of primary refractory patients, those who received 2nd line ASCT had increased second PFS (20.9 vs. 8.1 months, p<0.01) and second OS (74.7 vs. 31.3 months, p=0.02) compared to patients that did not. We conclude that early progression remains a significant factor for shorter OS in the current era, and salvage ASCT could be the most beneficial option for this population.