Introduction: Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have an unmet medical need. The objective of this trial was to assess the efficacy and toxicities of a novel triple immunotherapy regimen-pembrolizumab, low-dose cyclophosphamide, and maveropepimut-S (MVP-S). This regimen was designed to activate tumor-specific T cells by targeting the tumor-associated antigen survivin with MVP-S and reducing two important T cell inhibitory pathways: T cell exhaustion and regulatory T cells with pembrolizumab and metronomic cyclophosphamide, respectively.
Methods: This was a single-arm Phase II clinical trial in 25 participants with R/R DLBCL-SPiReL trial (NCT03349450).
Results: The median overall survival was 10.1 months and a third of participants survived over 2 years. Enhanced long-term survival was associated with favorable clinical characteristics and enhanced immune reactivity, as assessed by ELISpot and ISR-immune reactive responses. The regimen was well-tolerated with minimal Grade 3-4 toxicities.
Conclusion: Combination immunotherapy regimens such as this could offer a promising alternative to other treatments with significant toxicities for select patients.
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http://dx.doi.org/10.1002/jha2.1062 | DOI Listing |
Blood
January 2025
University of Chicago, Chicago, Illinois, United States.
Most diffuse large B-cell lymphoma (DLBCL) patients treated with immunotherapies such as bispecific antibodies (BsAb) or chimeric antigen receptor (CAR) T cells fail to achieve durable treatment responses, underscoring the need for a deeper understanding of mechanisms that regulate the immune environment and response to treatment. Here, an integrative, multi-omic approach was applied to multiple large independent datasets in order to characterize DLBCL immune environments, and to define their association with tumor cell-intrinsic genomic alterations and outcomes to CD19-directed CAR T-cell and CD20 x CD3 BsAb therapies. This approach effectively segregated DLBCLs into four immune quadrants (IQ) defined by cell-of-origin and immune-related gene set expression scores.
View Article and Find Full Text PDFIntroduction: Patients with relapsed/refractory diffuse large B-cell lymphoma (R/R DLBCL) have an unmet medical need. The objective of this trial was to assess the efficacy and toxicities of a novel triple immunotherapy regimen-pembrolizumab, low-dose cyclophosphamide, and maveropepimut-S (MVP-S). This regimen was designed to activate tumor-specific T cells by targeting the tumor-associated antigen survivin with MVP-S and reducing two important T cell inhibitory pathways: T cell exhaustion and regulatory T cells with pembrolizumab and metronomic cyclophosphamide, respectively.
View Article and Find Full Text PDFJ Transl Med
January 2025
Department of Hematology, Tianjin First Central Hospital, Tianjin, China.
Chimeric antigen receptor (CAR) T-cell therapy plays a critical role in the treatment of B-cell hematologic malignancies. The combination of PD-1 inhibitors and CAR-T has shown encouraging results in treating patients with relapsed/refractory (R/R) diffuse large B-cell lymphoma (DLBCL). However, there are still cases where treatment is ineffective.
View Article and Find Full Text PDFRecenti Prog Med
January 2025
Divisione di Ematologia e terapie cellulari, Irccs Ospedale Policlinico San Martino, Genova.
CAR-T therapy (chimeric antigen receptor T-cell) has revolutionized the prognosis of patients with diffuse large B-cell lymphoma (DLBCL) that have relapsed or are refractory to conventional chemotherapies. In particular, patients who have relapsed or are refractory to two lines of therapy are patients who have a poor prognosis. The advent of CAR-T immunotherapy is an innovative approach with which we can give hope of recovery even in the case of refractory disease, even for patients who are not candidates for high-dose therapies, for example due to age.
View Article and Find Full Text PDFLeuk Lymphoma
January 2025
Department of Neuro-oncology, Cancer Center, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.
Patients with relapsed/refractory primary central nervous system lymphoma (R/R PCNSL) usually have a poor prognosis and limited treatment options. We respectively reviewed 38 patients with R/R PCNSL treated with zanubrutinib-based regimens in our center. The overall response rate, complete response rate and disease control rate were 76.
View Article and Find Full Text PDFEnter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!