Prognostic factors in 448 newly diagnosed multiple myeloma receiving bortezomib-based induction: impact of ASCT, transplant refusal and high-risk MM.

In Hong Kong, newly diagnosed multiple myeloma (NDMM) receives bortezomib-based triplet induction. Upfront autologous stem cell transplant (ASCT) is offered to transplant eligible (TE) patients (NDMM ≤ 65 years of age), unless medically unfit (TE-unfit) or refused (TE-refused). Data was retrieved for 448 patients to assess outcomes. For the entire cohort, multivariate analysis showed that male gender (p = 0.006), international staging system (ISS) 3 (p = 0.003), high lactate dehydrogenase (LDH) (p = 7.6 × 10-7) were adverse predictors for overall survival (OS), while complete response/ near complete response (CR/nCR) post-induction (p = 2.7 × 10-5) and ASCT (p = 4.8 × 10-4) were favorable factors for OS. In TE group, upfront ASCT was conducted in 252 (76.1%). Failure to undergo ASCT in TE patients rendered an inferior OS (TE-unfit p = 1.06 × 10-8, TE-refused p = 0.002) and event free survival (EFS) (TE-unfit p = 0.00013, TE-refused p = 0.002). Among TE patients with ASCT, multivariate analysis showed that age ≥ 60 (p = 8.9 × 10-4), ISS 3 (p = 0.019) and high LDH (p = 2.6 × 10-4) were adverse factors for OS. In those with high-risk features (HR cytogenetics, ISS 3, R-ISS 3), ASCT appeared to mitigate their adverse impact. Our data reaffirmed the importance of ASCT. The poor survival inherent with refusal of ASCT should be recognized by clinicians. Finally, improved outcome with ASCT in those with high-risk features warrant further studies.

The impact of bortezomib-based induction in newly diagnosed multiple myeloma with chromosome 1q21 gain.

Introduction: Bortezomib has been reported to favourably impact the outcomes of t(4;14) and del(17p) in multiple myeloma (MM), but its impact on gain 1q (+1q) is unknown. Methods: To address this, 250 patients treated with bortezomib-based induction were analysed. All myeloma samples had fluorescence in situ hybridization (FISH) performed on CD138-sorted bone marrow aspirate, and plasma cells were analysed using DNA probes specific for the following chromosomal aberrations: del(13q14), del(17p), t(14;16), t(4;14), and +1q. Presence of +1q was defined as the presence of at least three copies of 1q21 at the cut off level of 20% of bone marrow plasma cells. Results: +1q identified in 167 (66.8%) and associated with t(4;14) and high lactate dehydrogenase (LDH). +1q was not associated with response rate but shorter event-free survival (EFS) (median EFS 35 vs 55 months, p = 0.05) and overall survival (OS) (median OS 74 vs 168 months, p = 0.00025). Copy number and clone size did not impact survival. Multivariate analysis showed +1q was an independent adverse factor for OS together with International Staging System (ISS)3, high LDH, del(17p) and t(4;14). When a risk score of 1 was assigned to each independent adverse factor, OS was shortened incrementally by a risk score from 0 to 4. Post-relapse/progression survival was inferior in those with +1q (median 60 vs 118 months, p = 0.000316). Autologous stem cell transplantation (ASCT) improved OS for those with +1q (median OS 96 vs 49 months, p = 0.000069). Conclusion: +1q is an adverse factor for OS in MM uniformly treated with bortezomib-based induction but was partially mitigated by ASCT. A risk scoring system comprising +1q, LDH, high-risk FISH, and ISS is a potential tool for risk stratification in MM.