Autologous stem cell transplantation after anti-PD-1 therapy for multiply relapsed or refractory Hodgkin lymphoma

Abstract

Autologous stem cell transplantation (ASCT) can be curative for patients with relapsed/refractory Hodgkin lymphoma (HL). Based on studies suggesting that anti-PD-1 monoclonal antibodies (mAbs) can sensitize patients to subsequent chemotherapy, we hypothesized that anti-PD-1 therapy before ASCT would result in acceptable outcomes among high-risk patients who progressed on or responded insufficiently to ≥1 salvage regimen, including chemorefractory patients who are traditionally considered poor ASCT candidates. We retrospectively identified 78 HL patients who underwent ASCT after receiving an anti-PD-1 mAb (alone or in combination) as third-line or later therapy across 22 centers. Chemorefractory disease was common, including 42 patients (54%) refractory to ≥2 consecutive systemic therapies immediately before anti-PD-1 treatment. Fifty-eight (74%) patients underwent ASCT after anti-PD-1 treatment, while 20 patients (26%) received additional therapy after PD-1 blockade and before ASCT. Patients received a median of 4 systemic therapies (range, 3-7) before ASCT, and 31 patients (41%) had a positive pre-ASCT positron emission tomography (PET) result. After a median post-ASCT follow-up of 19.6 months, the 18-month progression-free survival (PFS) and overall survival were 81% (95% CI, 69-89) and 96% (95% confidence interval [CI], 87-99), respectively. Favorable outcomes were observed for patients who were refractory to 2 consecutive therapies immediately before PD-1 blockade (18-month PFS, 78%), had a positive pre-ASCT PET (18-month PFS, 75%), or received ≥4 systemic therapies before ASCT (18-month PFS, 73%), while PD-1 nonresponders had inferior outcomes (18-month PFS, 51%). In this high-risk cohort, ASCT after anti-PD-1 therapy was associated with excellent outcomes, even among heavily pretreated, previously chemorefractory patients.

How to choose first salvage therapy in Hodgkin lymphoma: traditional chemotherapy vs novel agents

“…3,11 A ret ro spec tive anal y sis in 78 patients who progressed on one or more sal vage reg i mens and who were treated with reg i mens containing CPI showed favor able results, with 59% of patients achiev ing a CMR and a post-ASCT PFS of 81% at 18 months. 23 This sug gests that treatment with CPI may improve chemosensitivity of pre vi ously chemorefractory dis ease. Interestingly, pre-ASCT CMR sta tus was not sig nif cantly prog nos tic for post-ASCT PFS in this cohort, suggesting a PR might be suf f cient for pro ceed ing to ASCT after CPI in this patient pop u la tion.…”

Case Report: PD-1 Blockade Combined Autologous Hematopoietic Stem Cell Transplantation With Modified BEAM Regimen Containing High-Dose Cytarabine to Treat R/R Hodgkin's Lymphoma

“…Additionally, in the chemotherapy regimen for R/R lymphoma, the DHAP regimen containing high-dose cytarabine is more efficient compared to non-Hodgkin's lymphoma (NHL) high-dose cytarabine, with both higher OS and PFS, thus increasing the efficacy of lymphoma (HL) treatment ( 7 ). Merryman et al ( 19 ) recently reported that PD-1 mAb bridged ASCT with conventional BEAM to treat R/R HL can make 18-month PFS reach 78%. Therefore, in the treatment of this patient, we reasonably combined the advantages of PD-1 and ASCT.…”

The Emerging Role of CAR T Cell Therapy in Relapsed/Refractory Hodgkin Lymphoma

“…In some cases, immune reprogramming ahead of transplant may lead to even better outcomes. Herrera and colleagues demonstrated that heavily pre-treated patients who received PD-1 therapy ahead of autologous stem cell transplant and responded had improved rates of progressionfree survival at 18 months compared to PD-1 non-responders (86% vs. 51%, [86]). Overall, more research is needed in order to clarify the potential benefits (i.e., increased graft vs. lymphoma effect) and risks (increased GVHD) associated with the use of CAR T cells and other immunomodulatory agents, such as PD-1 inhibitors, ahead of transplant [87].…”