Stem cell transplantation in multiple myeloma: impact of response failure with thalidomide or lenalidomide induction

Abstract

Autologous stem cell transplantation as a platform for multiple myeloma treatment is the standard of care for patients who can safely withstand the procedure. Before novel agents were introduced, onethird to one-half of patients did not achieve partial response at transplantation. Previous medical literature has shown that in this past era, absence of initial response to induction therapy had no impact on progression-free survival and overall survival after highdose therapy. Lack of response to initial induction did not preclude a good response after stem cell transplantation. With the introduction of novel agentsimmunomodulatory drugs and proteasome inhibitors-response rates with initial therapy are now between 70% and 100%. This retrospective study analyzes progression-free survival and overall survival in patients who do not have a partial response (never responded or progressed during continuous therapy) after induction therapy with a regimen that contains thalidomide or lenalidomide. Unlike patients in reports published previously-before immunomodulatory drugs-patients who do not achieve partial remission have a significantly shorter overall survival from transplantation (73.5 vs 30.4 months) and a shorter progression-free survival (22.1 vs 13.1 months; P < .001). Absence of a response to induction therapy with thalidomide or lenalidomide predicts a poorer outcome after high-dose therapy. (Blood. 2010;115:2348-2353)

Value of novel agents and intensive therapy for patients with multiple myeloma

“…In comparison with our previous study, we observed higher frequencies of remission with both novel therapies and HDT. Calculations of survival after a landmark of 1 year, and the infrequency of censored data, contributed to the more marked differences in survival now observed for patients with NR, PR and CR in comparison with our previous report; 9 these results supported further the conclusion of Lahuerta et al 19 and of Gertz et al 20 on the importance of CR and PR on survival. Persistent NR was the most immediate and ominous problem that prevailed in only 10% of patients treated with recent programs, whose survival remained short and similar to that described by Snapper 50 years ago for patients unable to receive effective therapy.…”

Early relapse post autologous transplant is a stronger predictor of survival compared with pretreatment patient factors in the novel agent era: analysis of the Singapore Multiple Myeloma Working Group

“…14 A number of studies since have further reported that achievement of CR or stringent CR was associated with improved long-term outcomes when compared with lesser degrees of response with NA induction. 4,7 Despite these reported associations, additional pretransplant salvage chemotherapy in patients who did not achieve PR post-induction did not improve OS or PFS, even when deeper pretransplant responses were achieved. 15 The different implications of post-induction response reported across studies may reflect differences in study population, underlying disease heterogeneity in myeloma or the weaker predictive value of post-induction response.…”

“…[4][5][6][7] However, the outcomes of the group of patients who respond are heterogeneous; some patients relapse within a year and have very poor survival despite achieving deep responses. [8][9][10] It is unknown whether depth of response or early loss of response is a more important predictor of survival as both factors have not been compared directly in studies.…”

Achievement of VGPR to induction therapy is an important prognostic factor for longer PFS in the IFM 2005-01 trial

“…[11][12][13][14] Nevertheless, the type of response achieved with novel agents as induction before ASCT might have an important prognostic impact. 15 Combinations that use novel agents, including bortezomibbased therapy, are currently evaluated as induction treatment before ASCT, with the objective of increasing the CR or CR plus VGPR rate both before and after ASCT. [16][17][18] In this setting, the recent phase 3 study by the Intergroupe Francophone du Myélome (IFM2005-01; NCT00200681) demonstrated the superiority of bortezomibdexamethasone induction before HDT-ASCT compared with vincristine-adriamycin-dexamethasone (VAD), the previous standard of care.…”