Τίτλος:
Efficacy and safety of durvalumab combined with daratumumab in daratumumab-refractory multiple myeloma patients
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Daratumumab is active both as a single agent and in combination with other agents in multiple myeloma (MM) patients. However, the majority of patients will develop daratumumab-refractory disease, which carries a poor prognosis. Since daratumumab also has immunomodulatory effects, addition of the PD-L1 blocking antibody durvalumab at the time of progression may reverse daratumumab-resistance. The efficacy and safety of daratumumab and durvalumab in daratumumab-refractory relapsed/refractory MM patients was evaluated in this prospective, single-arm phase 2 study (NCT03000452). None of the 18 enrolled patients achieved PR or better. The frequency of serious adverse events was 38.9%, with one patient experiencing an immune related adverse event (grade 2 hyperthyroidism). No infusion-related reactions were observed. Analysis of tumor-and immune cell characteristics was performed on bone marrow samples obtained at baseline and during treatment. Daratumumab combined with durvalumab reduced the frequency of regulatory T-cells and decreased the proportion of T-cells expressing LAG3 and CD8+ T-cells expressing TIM-3, without altering T-and NK-cell frequencies. Durvalumab did not affect tumor cell characteristics associated with daratumumab resistance. In conclusion, the addition of durvalumab to daratumumab following development of daratumumab-resistance was associated with an acceptable toxicity profile, but was not effective. This indicates that inhibition of the PD-1/PD-L1 signaling pathway at the time of daratumumab-resistance is insufficient to reverse daratumumab-resistance. © 2021 by the authors. Licensee MDPI, Basel, Switzerland.
Συγγραφείς:
Frerichs, K.A.
Verkleij, C.P.M.
Dimopoulos, M.A.
Marin Soto, J.A.
Zweegman, S.
Young, M.H.
Newhall, K.J.
Mutis, T.
van de Donk, N.W.C.J.
Περιοδικό:
Blood cancer journal
Λέξεις-κλειδιά:
aciclovir; ADP ribosyl cyclase/cyclic ADP ribose hydrolase 1; bortezomib; carfilzomib; cell protein; checkpoint kinase inhibitor; cyclophosphamide; daratumumab; diphenhydramine; durvalumab; elotuzumab; hepatitis A virus cellular receptor 2; immunomodulating agent; ixazomib; LAG3 protein; lenalidomide; melphalan; methylprednisolone; montelukast; paracetamol; pomalidomide; programmed death 1 ligand 1; programmed death 1 receptor; proteasome inhibitor; thalidomide; unclassified drug, adult; aged; anemia; anorexia; Article; backache; bone marrow; bone pain; cancer patient; cancer survival; CD8+ T lymphocyte; clinical article; common cold; drug dose reduction; drug efficacy; drug response; drug safety; drug targeting; dyspnea; edema; fatigue; female; fever; flow cytometry; herpes zoster; human; human cell; human tissue; hypercalcemia; hypertension; hyperthyroidism; hyperuricemia; hypothesis; immune response; infusion related reaction; kidney failure; male; multicenter study; multiple cycle treatment; multiple myeloma; natural killer cell; nausea; neuralgia; neutropenia; overall survival; pain; patient monitoring; phase 2 clinical trial; pneumonia; progression free survival; prospective study; protein expression; regulatory T lymphocyte; RNA sequencing; side effect; T lymphocyte; thrombocytopenia; upper respiratory tract infection
DOI:
10.3390/cancers13102452
