Impact of Autologous Hematopoietic Stem Cell Transplantation on Newly Diagnosed Multiple Myeloma with Different Cytogenetic Profiles: A Brazilian Unicentric Cohort
Authors: Cordeiro Maria Gabriella , Velloso Elvira D. R. P. , Leal Aline de Medeiros , Santos Joaquim Gasparini , Otuyama Leonardo , Ramos Evelin , Seguro Fernanda Salles , Atanasio Marcelo Junqueira , Pereira Thales D.M. , Rocha Vanderson , Martinez Gracia Aparecida 
Published: December 2024

Introduction: Multiple myeloma (MM) is a heterogeneous disease with acquired genetic abnormalities of clinical and prognostic importance. Survival has improved with the introduction of new drugs. Although access to new therapies in low- and middle-income countries is restricted, autologous hematopoietic stem cell transplantation (ASCT) is a viable option. The aim of this study was to evaluate the potential impact of ASCT acrossdifferent cytogenetic profiles in newly diagnosed MM.

Methods: Patients with MM according to IMWG 2014 criteria, diagnosed between January 2020 to December 2023, eligible for transplantation were included. First line therapy with a thalidomide-based regimen or a bortezomib-based regimen was used. Cytogenetic studies were performed by interphase fluorescence in situ hybridization (iFISH) with CD138 positive selection according to European Myeloma network (EMN) guidelines. Five probes (CKS1B and CDKN2C, RB1, FGFR3::IGH, IGH::MAF1, P53) were used complemented in few cases with the probe for t(11;14) CCND1::IGH and with t(14;20) MAFB::IGH. Categorization into high and standard risk followed the M-Smart 3.0 consensus. Overall survival (OS) and progression-free survival (PFS) were calculated from diagnosis to outcome (death or relapse) using the Kaplan-Meier curve and log-rank comparison.

Results: Ninety-two patients were evaluated. The median age was 58 (21-80) years, 3 patients above 70; 71% were men; ECOG ≥ 2 in 58%, subtypes IgG 63%, IgA 16%, light chain 15%, kappa 67%; Durie & Salmon IIIA 64%, IIIB 28%; ISS III 51%; R-ISS III 35%. Ninety-one patients have iFISH studies and according to M-Smart cytogenetic score, 38 patients were high-risk, 35 standard and 19 could not have risk evaluated. The cytogenetic abnormalities observed were: deletion RB1 40% (31/77); gain CSK1B in 36% (33/91); t(11;14) in 30% (9/30), deletion CDKN2C in 11% (10/91), deletion 17p in 8% (7/87); t(4;14) in 6.7% (6/89); and t(14;16)/(14/20) in 2.7% (2/74). Sixty patients (65%) received a triple thalidomide-based regimen and 32 (35%) a triple bortezomib-based regimen.

OS for the entire cohort was 3.8 years; FPS, 2.6 years. Only 27% (25/92) underwent ASCT. OS in 4 years for patients who underwent ASCT compared to those who were not submitted to transplant was, respectively, not reached and 3.8 years (p&lt;0.01). PFS was 2.1 years for no transplant and not reached for transplanted patients, respectively (p&lt;0,01).

The OS and PFS in the global cohort for high and standard cytogenetic risk did not reach statistical significance. Seventy-three patients were evaluated for survival according to ASCT and cytogenetic risk. Twenty-five patients belong to high risk and do not undergo ASCT, 26 patients were standard risk and not undergo ASCT, 13 patients were high risk and underwent ASCT, and 9 were standard risk and also underwent ASCT. OS and PFS were 1.5 years and 1.1 years for high risk and no ASCT(p=0.0022; p=0.034). The same result is also reflected in the gain of CKS1B group, where OS in patients who underwent ASCT were not reached and those who did not undergo ASCT were 1.6 years (p=0.014).

Conclusion: Transplantation has a significant impact on the survival of MM patients without free access to new drugs. Our work reinforces the importance of ASCT in patients with high-risk cytogenetic features, which constitute nearly 50% of our cohort.