A Phase II, Open-Label Study of Lenalidomide and Dexamethasone Followed by Donor Lymphocyte Infusions in Relapsed Multiple Myeloma Following Upfront Allogeneic Stem Cell Transplant
Background: To date, the only potential curative treatment for multiple myeloma (MM) remains allogeneic (allo) hematopoietic cell transplant (HCT), although, most patients will eventually relapse. In relapsed patients, donor lymphocyte infusions (DLIs) have been reported to control disease, but the...
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MDPI AG
2024-11-01
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| Series: | Current Oncology |
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| Online Access: | https://www.mdpi.com/1718-7729/31/11/535 |
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| author | Richard LeBlanc Stéphanie Thiant Rafik Terra Imran Ahmad Jean-Sébastien Claveau Nadia Bambace Léa Bernard Sandra Cohen Jean-Sébastien Delisle Silvy Lachance Thomas Kiss Denis-Claude Roy Guy Sauvageau Jean Roy |
| author_facet | Richard LeBlanc Stéphanie Thiant Rafik Terra Imran Ahmad Jean-Sébastien Claveau Nadia Bambace Léa Bernard Sandra Cohen Jean-Sébastien Delisle Silvy Lachance Thomas Kiss Denis-Claude Roy Guy Sauvageau Jean Roy |
| author_sort | Richard LeBlanc |
| collection | DOAJ |
| description | Background: To date, the only potential curative treatment for multiple myeloma (MM) remains allogeneic (allo) hematopoietic cell transplant (HCT), although, most patients will eventually relapse. In relapsed patients, donor lymphocyte infusions (DLIs) have been reported to control disease, but the optimal strategy prior to and doses of DLIs remain unclear. With this study (NCT03413800), we aimed to investigate the efficacy and toxicity of lenalidomide and dexamethasome (Len/Dex) followed by escalating pre-determined doses of DLIs in MM patients who relapsed after allo HCT. Methods: Patients aged 18–65 years with relapsed MM following upfront tandem autologous (auto)/allo HCT were eligible. Treatment consisted of six cycles of Len/Dex followed by three standardized doses of DLIs: 5 × 10<sup>6</sup> CD3+/kg, 1 × 10<sup>7</sup>/kg and 5 × 10<sup>7</sup>/kg every 6 weeks. Bone marrow minimal measurable disease (MRD) using flow cytometry (10<sup>−5</sup>) was performed at enrolment, then every 3 months for 2 years or until disease progression, in a subset of patients. The primary endpoint was efficacy as measured by progression-free survival (PFS) at 2 years following Len/Dex/DLIs. Secondary objectives were safety including GVHD, response including MRD status and overall survival (OS). Results: A total of 22 patients participated in this study, including 62% with high-risk cytogenetics. With a median follow-up of 5.3 years (range: 4.1–6.1), PFS and OS were 26.5% (95% CI: 10.4–45.9%) and 69.2% (95% CI: 43.3–85.1%), respectively. Overall, the best responses achieved post-Len/Dex + DLIs were complete remission in 9.1%, very good partial response in 50%, and progressive disease in 40.9%. Among the nine patients tested for MRD, only two achieved a negative status after receiving DLIs. Six patients died, all due to disease progression. No acute GVHD was observed after DLIs. We report a very low incidence of moderate/severe chronic GVHD of 18.2% with no need for systemic immunosuppressants one year after diagnosis. No unexpected adverse events were observed. Interestingly, a positive correlation between response to Len/Dex re-induction and response to DLIs was found (<i>p</i> = 0.0032). Conclusions: Our findings suggest that Len/Dex/DLIs in second line treatment after upfront tandem auto/allo HCT in relapsed MM patients remains feasible and safe. With a potential correlation between induction chemotherapy and DLI responses, more potent induction regimens together with higher doses of DLIs should be considered in the future. |
| format | Article |
| id | doaj-art-9acbe03a7d374dee9757b677dc3cfdee |
| institution | OA Journals |
| issn | 1198-0052 1718-7729 |
| language | English |
| publishDate | 2024-11-01 |
| publisher | MDPI AG |
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| series | Current Oncology |
| spelling | doaj-art-9acbe03a7d374dee9757b677dc3cfdee2025-08-20T02:08:14ZengMDPI AGCurrent Oncology1198-00521718-77292024-11-0131117258727410.3390/curroncol31110535A Phase II, Open-Label Study of Lenalidomide and Dexamethasone Followed by Donor Lymphocyte Infusions in Relapsed Multiple Myeloma Following Upfront Allogeneic Stem Cell TransplantRichard LeBlanc0Stéphanie Thiant1Rafik Terra2Imran Ahmad3Jean-Sébastien Claveau4Nadia Bambace5Léa Bernard6Sandra Cohen7Jean-Sébastien Delisle8Silvy Lachance9Thomas Kiss10Denis-Claude Roy11Guy Sauvageau12Jean Roy13Division of Hematology, Oncology and Transplantation, Department of Medicine, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, CanadaCentre de Recherche, Hôpital Maisonneuve-Rosemont, Montréal, QC H1T 2M4, CanadaDivision of Hematology, Oncology and Transplantation, Department of Medicine, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, CanadaDivision of Hematology, Oncology and Transplantation, Department of Medicine, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, CanadaDivision of Hematology, Oncology and Transplantation, Department of Medicine, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, CanadaDivision of Hematology, Oncology and Transplantation, Department of Medicine, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, CanadaDivision of Hematology, Oncology and Transplantation, Department of Medicine, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, CanadaDivision of Hematology, Oncology and Transplantation, Department of Medicine, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, CanadaDivision of Hematology, Oncology and Transplantation, Department of Medicine, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, CanadaDivision of Hematology, Oncology and Transplantation, Department of Medicine, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, CanadaDivision of Hematology, Oncology and Transplantation, Department of Medicine, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, CanadaDivision of Hematology, Oncology and Transplantation, Department of Medicine, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, CanadaDivision of Hematology, Oncology and Transplantation, Department of Medicine, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, CanadaDivision of Hematology, Oncology and Transplantation, Department of Medicine, Maisonneuve-Rosemont Hospital, Montréal, QC H1T 2M4, CanadaBackground: To date, the only potential curative treatment for multiple myeloma (MM) remains allogeneic (allo) hematopoietic cell transplant (HCT), although, most patients will eventually relapse. In relapsed patients, donor lymphocyte infusions (DLIs) have been reported to control disease, but the optimal strategy prior to and doses of DLIs remain unclear. With this study (NCT03413800), we aimed to investigate the efficacy and toxicity of lenalidomide and dexamethasome (Len/Dex) followed by escalating pre-determined doses of DLIs in MM patients who relapsed after allo HCT. Methods: Patients aged 18–65 years with relapsed MM following upfront tandem autologous (auto)/allo HCT were eligible. Treatment consisted of six cycles of Len/Dex followed by three standardized doses of DLIs: 5 × 10<sup>6</sup> CD3+/kg, 1 × 10<sup>7</sup>/kg and 5 × 10<sup>7</sup>/kg every 6 weeks. Bone marrow minimal measurable disease (MRD) using flow cytometry (10<sup>−5</sup>) was performed at enrolment, then every 3 months for 2 years or until disease progression, in a subset of patients. The primary endpoint was efficacy as measured by progression-free survival (PFS) at 2 years following Len/Dex/DLIs. Secondary objectives were safety including GVHD, response including MRD status and overall survival (OS). Results: A total of 22 patients participated in this study, including 62% with high-risk cytogenetics. With a median follow-up of 5.3 years (range: 4.1–6.1), PFS and OS were 26.5% (95% CI: 10.4–45.9%) and 69.2% (95% CI: 43.3–85.1%), respectively. Overall, the best responses achieved post-Len/Dex + DLIs were complete remission in 9.1%, very good partial response in 50%, and progressive disease in 40.9%. Among the nine patients tested for MRD, only two achieved a negative status after receiving DLIs. Six patients died, all due to disease progression. No acute GVHD was observed after DLIs. We report a very low incidence of moderate/severe chronic GVHD of 18.2% with no need for systemic immunosuppressants one year after diagnosis. No unexpected adverse events were observed. Interestingly, a positive correlation between response to Len/Dex re-induction and response to DLIs was found (<i>p</i> = 0.0032). Conclusions: Our findings suggest that Len/Dex/DLIs in second line treatment after upfront tandem auto/allo HCT in relapsed MM patients remains feasible and safe. With a potential correlation between induction chemotherapy and DLI responses, more potent induction regimens together with higher doses of DLIs should be considered in the future.https://www.mdpi.com/1718-7729/31/11/535allogeneic hematopoietic cell transplantdonor lymphocyte infusionminimal measurable diseasemultiple myeloma |
| spellingShingle | Richard LeBlanc Stéphanie Thiant Rafik Terra Imran Ahmad Jean-Sébastien Claveau Nadia Bambace Léa Bernard Sandra Cohen Jean-Sébastien Delisle Silvy Lachance Thomas Kiss Denis-Claude Roy Guy Sauvageau Jean Roy A Phase II, Open-Label Study of Lenalidomide and Dexamethasone Followed by Donor Lymphocyte Infusions in Relapsed Multiple Myeloma Following Upfront Allogeneic Stem Cell Transplant Current Oncology allogeneic hematopoietic cell transplant donor lymphocyte infusion minimal measurable disease multiple myeloma |
| title | A Phase II, Open-Label Study of Lenalidomide and Dexamethasone Followed by Donor Lymphocyte Infusions in Relapsed Multiple Myeloma Following Upfront Allogeneic Stem Cell Transplant |
| title_full | A Phase II, Open-Label Study of Lenalidomide and Dexamethasone Followed by Donor Lymphocyte Infusions in Relapsed Multiple Myeloma Following Upfront Allogeneic Stem Cell Transplant |
| title_fullStr | A Phase II, Open-Label Study of Lenalidomide and Dexamethasone Followed by Donor Lymphocyte Infusions in Relapsed Multiple Myeloma Following Upfront Allogeneic Stem Cell Transplant |
| title_full_unstemmed | A Phase II, Open-Label Study of Lenalidomide and Dexamethasone Followed by Donor Lymphocyte Infusions in Relapsed Multiple Myeloma Following Upfront Allogeneic Stem Cell Transplant |
| title_short | A Phase II, Open-Label Study of Lenalidomide and Dexamethasone Followed by Donor Lymphocyte Infusions in Relapsed Multiple Myeloma Following Upfront Allogeneic Stem Cell Transplant |
| title_sort | phase ii open label study of lenalidomide and dexamethasone followed by donor lymphocyte infusions in relapsed multiple myeloma following upfront allogeneic stem cell transplant |
| topic | allogeneic hematopoietic cell transplant donor lymphocyte infusion minimal measurable disease multiple myeloma |
| url | https://www.mdpi.com/1718-7729/31/11/535 |
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