TY - JOUR
T1 - An Allogeneic Multiple Myeloma GM-CSF-Secreting Vaccine with Lenalidomide Induces Long-term Immunity and Durable Clinical Responses in Patients in Near Complete Remission
AU - Biavati, Luca
AU - Ann Huff, Carol
AU - Ferguson, Anna
AU - Sidorski, Amy
AU - Stevens, M. Amanda
AU - Rudraraju, Lakshmi
AU - Zucchinetti, Cristina
AU - Abbas Ali, Syed
AU - Imus, Philip
AU - Gocke, Christian B.
AU - Gittelman, Rachel M.
AU - Johnson, Sarah
AU - Sanders, Catherine
AU - Vignali, Marissa
AU - Gandhi, Anita
AU - Ye, Xiaobu
AU - Noonan, Kimberly A.
AU - Borrello, Ivan
N1 - Publisher Copyright:
© 2021 American Association for Cancer Research.
PY - 2021/12/15
Y1 - 2021/12/15
N2 - Purpose: This proof-of-principle clinical trial evaluated whether an allogeneic multiple myeloma GM-CSF-secreting vaccine (MMGVAX) in combination with lenalidomide could deepen the clinical response in patients with multiple myeloma in sustained near complete remission (nCR). Patients and Methods: Fifteen patients on lenalidomide were treated with MM-GVAX and pneumococcal conjugate vaccine (PCV; Prevnar) at 1, 2, 3, and 6 months. Results: Eight patients (53.3%) achieved a true CR. With a median follow-up of 5 years, the median progression-free survival had not been reached, and the median overall survival was 7.8 years from enrollment. MM-GVAX induced clonal T-cell expansion and measurable cytokine responses that persisted up to 7 years in all patients. At baseline, a higher minimal residual disease was predictive of early relapse. After vaccination, a lack of both CD27_DNAM1_CD8 T cells and antigen-presenting cells was associated with disease progression. Conclusions: MM-GVAX, along with lenalidomide, effectively primed durable immunity and resulted in long-term disease control, as suggested by the reappearance of a detectable, fluctuating Mspike without meeting the criteria for clinical relapse. For patients in a nCR, MM-GVAX administration was safe and resulted in prolonged clinical responses.
AB - Purpose: This proof-of-principle clinical trial evaluated whether an allogeneic multiple myeloma GM-CSF-secreting vaccine (MMGVAX) in combination with lenalidomide could deepen the clinical response in patients with multiple myeloma in sustained near complete remission (nCR). Patients and Methods: Fifteen patients on lenalidomide were treated with MM-GVAX and pneumococcal conjugate vaccine (PCV; Prevnar) at 1, 2, 3, and 6 months. Results: Eight patients (53.3%) achieved a true CR. With a median follow-up of 5 years, the median progression-free survival had not been reached, and the median overall survival was 7.8 years from enrollment. MM-GVAX induced clonal T-cell expansion and measurable cytokine responses that persisted up to 7 years in all patients. At baseline, a higher minimal residual disease was predictive of early relapse. After vaccination, a lack of both CD27_DNAM1_CD8 T cells and antigen-presenting cells was associated with disease progression. Conclusions: MM-GVAX, along with lenalidomide, effectively primed durable immunity and resulted in long-term disease control, as suggested by the reappearance of a detectable, fluctuating Mspike without meeting the criteria for clinical relapse. For patients in a nCR, MM-GVAX administration was safe and resulted in prolonged clinical responses.
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U2 - 10.1158/1078-0432.CCR-21-1916
DO - 10.1158/1078-0432.CCR-21-1916
M3 - Article
C2 - 34667029
AN - SCOPUS:85122395505
SN - 1078-0432
VL - 27
SP - 6696
EP - 6708
JO - Clinical Cancer Research
JF - Clinical Cancer Research
IS - 24
ER -