Background: High-dose chemotherapy (HDT) followed by autologous haematopoietic stem cell transplantation (ASCT) is the standard consolidation therapy for eligible patients with newly diagnosed Multiple myeloma (MM).Many trials have demonstrated the superiority of ASCT over non-intensive approaches, patients had received high-dose chemotherapy with melphalan at a dose of 200mg/m 2 (Mel200).Some studies had associated Mel200 with increased toxicities Collaboration to Collect Autologous Transplant Outcomes in Lymphoma and Myeloma (CALM) study showed that outcomes were similar in Mel140 vs Mel200 when patients were in partial response (PR) or better. In this study,we looked at the outcomes and safety of conditioning regimen used at two different doses of Melphalan for patients who had achieved PR.

Methods: This retrospective study comprised of patients treated in our hospital between January 2013 and December 2020. Patients with MM who had achieved PR, very good partial response (VGPR) or complete response (CR) as per standard IMWG response criteria at ASCT were included . Mel 140 and Mel200 were used for consolidation treatment. Patients who received other doses were excluded. Variables assessing safety namely neutrophil engraftment (defined as first of 3 successive days with an absolute neutrophil count of >/=0.5x10 9/L after post-transplant nadir), platelet engraftment (defined as first of 3 consecutive days with count >/=20 x10 9/L in absence of platelet transfusion for 3 days), days of hospital stay, quantity of PRBC and platelets, febrile neutropenia episodes and number and duration of antibiotic therapy and variables assessing outcome namely Progression Free Survival (PFS) were compared between the two groups. Categorical variables were analysed using Chi-Square/Fisher test, exact and continuous variables using student's T-test /Mann-Whitney Test. Kaplan-Meier (KM) plot was generated to depict PFS. A Breslow test was run to determine difference between survival distributions. All analysis used SPSS 22 version and a p value of < 0.05 was considered statistically significant.

Results: The study included fifty seven patients (n=57) who underwent ASCT with a median follow up of 110 ± 12.3 months . Male / Female ratio was 1.48:1 and the mean age was 52.4 (28-66).Patient characteristics are described in table 1. The disease status at time of transplant was PR 16(28%), VGPR 25 (43.8%) and CR 16 (28%). GCSF alone was used for stem cell mobilisation in 29 patients (50.8%), GCSF + Plerixafor in 26 (45.6%), GCSF + cyclophosphamide in 2 (3.5%). The median CD34 count was 5.2 (1.49 - 19) x 10 6cells/ml. The median time to neutrophil engraftment was 9.5 (8 - 21) days and to platelet engraftment was 10.5 (7 - 40) days . The estimated PFS by KM plots showed a median survival of 42.5 +/-5.2 months. On comparative analysis of patients who received Mel200 vs Mel140, both the groups had similar demographic characteristics and disease outcomes (Table 1).Patients who received Mel 140 received significantly less number of packed red blood cell units (PRBC) [1 (0-1) vs 2 (1-5), P = 0.022] and platelets [9 (1-5) Vs 10(1-19), P<001].These patients also had faster platelet engraftment (P =0.004) and lower incidence of Mucositis[9.7% vs 61.5%, P < 001] reflecting a favourable toxicity profile of this dose. However, the lower dose does not seem to affect disease outcome since PFS was similar in Mel 200 and Mel 140 (42.6 ± 4.8) Vs (42.8 ± 6.3) months [Figure 1]

Conclusion: For patients with MM who achieved PR , VGPR and CR prior to ASCT, Mel140 had similar PFS as Mel200 with lesser toxicities like mucositis, faster platelet engraftment and reduced blood product and antibiotic usage . Even though the study is limited by a smaller cohort and retrospective design, the results suggest the need for a prospective randomised controlled trials to compare Mel140 and Mel200 in patients achieving PR or more prior to ASCT.

Figure 1
Figure 1.
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Disclosures

No relevant conflicts of interest to declare.

© 2021 by The American Society of Hematology
2021
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