Multiagent Chemotherapy Versus Single Agent Melphalan for Condition Regimen for Autologous Stem Cell Transplant in Hodgkin Lymphoma

INTRODUCTION:

The outcome of Hodgkin lymphoma (HL) has improved in recent years with the incorporation of targeted therapy and checkpoint inhibitors. However, a significant number of patients have refractory disease or relapse after the frontline. Salvage therapy followed by autologous stem cell transplant (SCT) is the standard of care for those patients. Global shortage and interruption of medication availability can affect the choice of treatment. Here, we compare the outcome of patients who received multiagent chemotherapy versus single-agent melphalan as conditioning chemotherapy for SCT in patients who responded to salvage therapy.

METHODS:

We retrospectively evaluated 60 patients who underwent SCT at King Fahad Specialist Hospital from (2015 - 2023). The objectives were to compare progression-free survival (PFS), overall survival (OS), transplant toxicity, and length of hospital stay between patients receiving multiagent chemotherapy [BEAM (carmustine, etoposide, cytarabine, melphalan), BuEMel (Busulfan, etoposide, melphalan), BuMel (Busulfan, melphalan) Or BeEAM (Bendamustine, etoposide, cytarabine, melphalan)] versus single agent melphalan.

Independent sample t-test, Pearson Chi-square test or Fisher Exact test as appropriate were used to compare clinical characteristics between single melphalan vs multiagent chemotherapy group. The overall survival and progression free survival were evaluated using the Kaplan-Meier estimator, and compared between the two groups using the log-rank test. A “P” value <0.05 (two-tailed) were considered statistically significant.

Results:

Of sixty patients included in our analysis, 60% were male, and the median age at transplant was 28.4 years with standard deviation (SD) of 10.3; 27 patients (45%) received multiagent chemotherapy, 33 patients (55%) received single-agent melphalan, 83% patients had either primary refractory or relapsed within one year, and extranodal disease was present in 27.6% of the patients.

More patients achieved complete metabolic response (CMR) before transplant in the single melphalan group compared to the multiagent chemotherapy group (87.9% vs 51.9%, p=0.002). Primary refractory and early relapse patients were 75.8% and 92.6% (p=0.162), and extranodal at relapse were 18.8% and 38.5% (P= 0.095) for the melphalan group and multiagent chemotherapy group respectively, advance stage at relapse were 21.9% and 18.5% (P= 0.75) and IPS ≥4 was 12.1% and 7.4% (P= 0.68) for melphalan group and multiagent chemotherapy group respectively.

Incidence of all grade mucositis was 15.2% vs. 48.1% (P= 0.01), and febrile neutropenia was 15.2% vs. 25.9% (p= 0.34) for the single-agent melphalan group and multiagent group, respectively. The mean time for neutrophil engraftment in the melphalan group was 11.3 ± SD (2.3) days vs. 10.7 ± SD (1.9) days in multiagent groups (P= 0.266), and mean time for platelets engraftment was 13.5 ± SD (2.9) days for single-agent melphalan vs 11.2 ± SD (3.1) days in the multiagent group (p= 0.004).

The Melphalan group had fewer days of admission as most of them were treated as outpatients except for six patients who were admitted during the transplant period for complications, namely febrile neutropenia, and mucositis. The 5-year PFS was 48.6% vs. 60.4% (p=0.56), and the 5-year OS was 88% vs. 100% (p=0.221) in the single-agent Melphalan group and multiagent group, respectively.

CONCLUSIONS:

Our results did not show any statistical difference in PFS or OS between the two groups. Despite that, more patients achieved CMR prior to SCT in the single melphalan group. There is a trend toward favoring the multiagent condition chemotherapy group. Because of the small number of the two cohorts and the low event rate between the two, we propose multicenter or registry collaboration.

No relevant conflicts of interest to declare.