Boisjoly J-A, et al. ASH 2017:2022

Impact of carmustine substitution for bendamustine in the conditioning regimen prior to aHSCT for the treatment of lymphoma

Background

At the Hôpital Maisonneuve-Rosemont (HMR) in Montreal, Quebec, bendamustine has recently replaced carmustine (BCNU) in chemotherapy-based conditioning regimens for autologous hematopoietic stem cell transplantation (aHSCT) in patients with lymphoma. At ASH 2017, the team at HMR presented a study comparing the efficacy, toxicity, and pharmaco-economic impacts of this substitution.1

Study design

  • Between January 2012 and September 2016, the files of 146 consecutive patients who received an aHSCT for lymphoma at HMR were reviewed.
  • Patients were treated with a BCNU-containing conditioning regimen including either etoposide, cytarabine, and melphalan (BEAM) or etoposide, cytarabine, and cyclophosphamide (BEAC), between January 2012 and January 2015.
    • After this date patients were treated with the conditioning regimen consisting of bendamustine, etoposide, cytarabine, and melphalan (Benda-EAM).
  • Indications for aHSCT, eligibility criteria, treatment, and supportive care were identical for the two conditioning regimens being examined and followed the standard operating procedures of the transplant program at HMR (accredited by the Foundation for the Accreditation of Cellular Therapy).
  • The study analyzed clinical characteristics, parameters of engraftment, toxicities, post-transplant outcomes, and pharmaco-economical impact for the two groups being studied.

Key findings

  • The study analyzed 96 patients treated with BCNU-based regimens and 50 patients treated with the Benda-EAM regimen.

Clinical characteristics

  • The median age of patients was 55.5 years and 57.5 years in the BCNU and bendamustine groups, respectively.
  • In both groups of patients, the median Karnofsky grade was 90 and the median hematopoietic cell transplantation-specific comorbidity index was 1.
  • Of the patients with lymphoma studied, 43 patients (86%) in the Benda-EAM treatment group and 72 patients (75%) in the BCNU-based treatment group had non-Hodgkin lymphoma.
  • A higher frequency of complete remission pre-transplant was reported in the Benda-EAM versus BCNU-based arms (76% vs. 49%; p = 0.006).

Engraftment parameters

  • The median number of infused cluster of differentiation 34 cells was 5.26 x 106/kg in the BCNU arm and 4.88 x 106/kg in the bendamustine arm.
  • The median time for neutrophil engraftment (≥0.5 x 109/L) was 10 days in both arms, and for platelet engraftment (≥20 x 109/L) the median time was 16 days with the BCNU-based regimens and 18 days with the Benda-EAM regimen.
  • Granulocyte-colony stimulating factor was given for a median of five days in both groups.
  • Patients in the BCNU and bendamustine groups received a median of two units and one unit of red blood cells, and three units and four units of platelets, respectively.

Safety and Efficacy

  • A higher frequency of toxicities was reported with the Benda-EAM regimen compared to the BCNU-based regimens. (Table 1)
  • Only one case of transplant-related mortality was reported in the BCNU arm.
  • Post-transplant efficacy outcomes are presented in Table 2.
  • Overall survival (OS) for patients receiving the Benda-EAM conditioning regimen appeared to be non-inferior to the OS in patients who received BCNU-based conditioning regimens. (Figure 1)

Table 1. Toxicities associated with conditioning regimen

Table 2. Post-transplant outcomes

Figure 1. Overall survival

Pharmaco-economical assessment

  • The cost of the conditioning regimen was greater for BCNU-based regimens compared with the Benda-EAM regimen ($21,640.97 CDN vs. $11,305.61 CDN, respectively).
  • The cumulative cost of the Benda-EAM regimen was more favourable than the BCNU-based regimens ($104,750.05 CDN vs. $109,946.00 CDN, respectively), when considering cost of conditioning regimen, supportive care, and hospital stay. (Table 3)

Table 3. Pharmaco-economic assessment

Key conclusions

  • The Benda-EAM conditioning regimen resulted in increased toxicity and morbidity for aHSCT in patients with lymphoma compared to BCNU-based regimens; however, transplant-related mortality was not impacted.
  • To ensure patients are aware of increased toxicities, a specialized transplant team should be involved in care decisions.
  • OS for patients in the Benda-EAM arm appears superior to OS for patients receiving BCNU-based regimens, which may be partly explained by the more favourable disease status at the time of transplant for these patients.
  • Although longer follow-up and a larger sample size are needed to confirm these results, the current data suggest that Benda-EAM is an effective and less expensive alternative to BCNU-based conditioning regimens for patients with lymphoma receiving an aHSCT, albeit with slightly more toxicity.

Reference: 1. Boisjoly J-A, Bouchard P, Cohen S, et al. Impact of carmustine (BCNU) substitution for bendamustine in the conditioning regimen prior to autologous hematopoietic stem cell transplantation for the treatment of lymphoma. ASH Annual Meeting Abstracts 2017:2022.