Referral of responders with chemosensitive relapsed/refractory DLBCL to HCT associated with improved OS

Referral of patients with relapsed/refractory chemotherapy-sensitive diffuse B-cell lymphoma who achieved a partial or better response to transplantation resulted in improved overall survival compared with those who underwent additional lines of therapy.

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

Median OS in the hematopoietic cell transplantation (HCT) group, which includes those directly referred for HCT without second salvage, was 105.8 months (95% CI, 63-148) versus 14.5 months (95% CI, 0-44) in the second – rescue group (P = 0.035). Moreover, the estimated 3-year OS rate was 65% (95% CI, 51%-75%) in the HCT group versus 40% (95% CI, 21%-53%) in the second salvage group (P = 0.035). Receiving a second salvage regimen was associated with worse survival (HR, 2.57; 95% CI, 1.1-5.8; P = 0.023) along with older age (HR 1.04; 95% CI, 0.99-1.20; P = 0.064).

Notably, the 2 groups did not have significantly different CR rates, with the investigators reporting a rate of 66% in the HCT group versus 68% in the second salvage group (P = 0.86). Moreover, median progression-free survival was not reached (NR) in the transplant group compared to 10.2 months [95% CI, 7.1-12.3; P = .27]) in another rescue group. Three-year PFS rates were 54% vs. 44%. Neither International Prognostic Index (IPI) score nor disease status (primary refractory or relapsed) influenced PFS.

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

A multicenter retrospective study evaluated 197 patients with relapsed/refractory DLBCL who underwent HCT at 4 stem cell transplant centers from January 2008 to June 2018, of whom 69 had a partial response after first salvage therapy and were are 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, resulting in a higher IPI score at relapse. The majority of patients were male (62%) and the majority had primary refractory disease or relapsed lymphoma within 1 year of completion of treatment (70%).

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

Notably, patients who received a different second salvage regimen had a higher response rate (37%) than those who received a further cycle of their first regimen (10%), but this finding did not reach statistical significance (P = 0.16).

“Future studies should focus on better characterizing patient subgroups who may benefit from CAR-T or novel monoclonal antibodies versus 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 do not have access to CAR-T/novel antibody therapy due to logistical and economic constraints,” the researchers concluded.

Reference

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

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