Mitoxantrone Hydrochloride Liposome Combined with Polatuzumab Vedotin and Dexamethasone (MPD) Is Highly Effective and Well Tolerated As Bridging Therapy before Chimeric Antigen Receptor T-Cell Therapy for Relapsed/Refractory Diffuse Large B Cell Lymphoma

Background:

Increasing studies have proved that CD19 chimeric antigen receptor T-cell therapy (CAR-T) is a better choice for patients with primary refractory or heavily pretreated diffuse large B cell lymphoma (DLBCL). However, due to high tumor burden or rapid disease progression, bridging therapy is often implemented to control the disease and improve the patient status before CAR-T infusion. No optimal regimens have been defined for bridging therapy. Mitoxantrone Hydrochloride Liposome (Lipo-MIT) has been approved in China for treating relapsed/refractory T cell lymphoma, and several studies using Lipo-MIT based therapy have shown promising outcomes in relapsed/refractory DLBCL (R/R-DLBCL). In this retrospective study, we aimed to explore the efficacy and safety profiles of Lipo-MIT combined with polatuzumab vedotin and dexamethasone (MPD) as bridging therapy before CAR-T infusion in patients with R/R-DLBCL.

Methods:

Ten patients with R/R-DLBCL enrolled in a prospective clinical trial of CD19/ CD22 Bispecific CAR-T cell therapy (NCT06081478) received MPD regimen as bridging therapy, and herein we just reported the efficacy and safety profiles of the bridging MPD regimen retrospectively. Lipo-MIT was given at a dosage of 20-30 mg on day 1 (for elderly patients, 20 mg was preferred). Polatuzumab vedotin was given at the recommended dosage of 1.8 mg/kg on day 1, and dexamethasone was given at the dosage of 20 mg/d on day 1 to 4. Five out of the ten patients received rituximab in addition to MPD regimen. All patients received only one cycle of MPD bridging therapy and proceeded to lymphodepleting conditioning therapy when CAR-T cells were successfully manufactured. PET-CT or CT scan were done before lymphodepleting therapy to assess the efficacy of MPD regimen.

Results:

Six female and four male patients with a median age of 61 years old (22-71) were included in this retrospective analysis. The median prior treatment lines was three (2-5), and seven patients had primary refractory DLBCL, among whom four patients never responded to previous treatments. At the time of enrollment to this clinical trial of CD19/CD22 bispecific CAR-T cell therapy, eight patients had stage III-IV disease, and the median IPI score was four (1-5). Most patients had unsatisfactory performance status, with the median ECOG score being two (1-4). All patients completed one cycle of MPD with/without rituximab. Concerning the safety profiles, two patients had grade four neutropenia, and one had moderate anemia. One patient got COVID-19 infection and repeated fever. All adverse effects recovered after supportive care. Using PET-CT or CT scan, all ten patients got remission (one complete remission, and nine partial remission). Symptoms related to DLBCL obviously relieved, and the performance status improved for most patients, with the median ECOG score being one (1-2) before CAR-T infusion. All patients successfully proceeded to subsequent lymphodepleting therapy.

Conclusions:

MPD regimen was highly effective and well tolerated in patients with R/R-DLBCL who meant to receive CAR-T cell therapy, and could be used as bridging therapy to control disease and improve performance status to facilitate subsequent CAR-T infusion. Well-designed prospective clinical trials are needed to confirm our findings.

No relevant conflicts of interest to declare.

Mitoxantrone Hydrochloride Liposome (Lipo-MIT) has been approved in China for treating relapsed/refractory T cell lymphoma, and several studies using Lipo-MIT based therapy have shown promising outcomes in relapsed/refractory DLBCL (R/R-DLBCL). Thus, we will discuss the use of Lipo-MIT as bridging therapy for DLBCL as off-lable.