Referral of Responders With Chemo-Sensitive Relapsed/Refractory DLBCL to HCT Associated With Improved OS

Patients with chemotherapy-sensitive relapsed/refractory diffuse large B-cell lymphoma (DLBCL) who achieved a partial response (PR) or complete response (CR) and were referred to transplant vs additional lines of therapy appeared to have better overall survival (OS), according to data from a retrospective study published in the European Journal of Hematology.

Median OS in the hematopoietic cell transplantation (HCT) group, comprising those referred directly to HCT without a second salvage, was 105.8 months (95% CI, 63-148) vs 14.5 months (95% CI, 0-44) in the second-salvage group (P = .035). Moreover, the estimated 3-year OS rate was 65% (95% CI, 51%-75%) in the HCT group vs 40% (95% CI, 21%-53%) in the second-salvage group (P = .035). Receipt of a second salvage regimen was associated with inferior survival (HR, 2.57; 95% CI, 1.1-5.8; P = .023) along with older age (HR 1.04; 95% CI, 0.99-1.20; P = .064).

Notably, the 2 groups did not have substantially different CR rates, with investigators reporting a rate of 66% in the HCT group vs 68% in the second-salvage group (P = .86). Moreover, the median progression-free survival was not reached (NR) in the transplant group vs. 10.2 months [95% CI, 7.1-12.3; P = .27]) in the second salvage group. The 3-year PFS rates were 54% vs 44%, respectively. Neither International Prognostic Index (IPI) score nor disease status (primary refractory vs relapsed) impacted PFS.

“Our study shows that referring patients with chemosensitive disease directly to transplant, whether in complete response or partial response, is associated with a better OS compared to receiving additional lines of therapy,” the investigators wrote. “Due to the fact that we lack established predictors for response to additional salvage regimens, we recommend proceeding directly to HCT in the case of chemosensitive disease and not deferring transplant to further improve lymphoma response.”

The multicenter retrospective study assessed 197 patients with relapsed/refractory DLBCL who underwent HCT in 4 stem cell transplant centers from January 2008 to June 2018, 69 of whom had a partial response after the first salvage therapy and were included in the analysis. The HCT group included 47 patients and the second-salvage group included 22.

The median age in the total study cohort was 60 years (range, 25-75). Most patients had stage III/IV disease with elevated lactate dehydrogenase, translating into a higher IPI score at relapse. Most patients were men (62%) and most had primary refractory disease or a recurrence of lymphoma within 1 year of completing treatment (70%).

All patients received rituximab (Rituxan) in combination with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), or an equivalent anthracycline-containing protocol, as frontline therapy. Patients in the second-salvage group received either a further cycle of the same frontline salvage regimen (n = 10; 46%), switched to a different regimen (n = 8; 36%), or got radiation therapy (n = 4; 18%).

Notably, patients who received a different second-salvage regimen had a higher response rate (37%) vs those who received a further cycle of their frontline regimen (10%), but this finding did not reach statistical significance (P = .16).

“Future studies should focus on better characterizing subgroups of patients who may benefit from CAR-T or novel monoclonal antibodies vs. those who may be more suitable for HCT. This conclusion is relevant even in the CAR T era and could be applied to patients who lack access to CAR-T/novel antibodies therapy due to logistic and economic limitations,” the investigators concluded.

Reference

Shargian L, Amit O, Bernstine H, et al. The role of additional chemotherapy prior to autologous HCT in patients with relapse/refractory DLBCL in partial remission­–a retrospective multicenter study. Eur J Haematol. Published online October 17, 2022. doi:10.1111/ejh.13884