Avelumab, a PD-L1 Inhibitor, in Combination with Hypofractionated Radiotherapy and the Abscopal Effect in Relapsed Refractory Multiple Myeloma

Author:

Kazandjian Dickran12,Dew Alexander13,Hill Elizabeth1,Ramirez Elizabeth Gil4,Morrison Candis1,Mena Esther5,Lindenberg Liza5,Yuan Constance6,Maric Irina7,Wang Hao-Wei6,Calvo Katherine7,Dulau-Florea Alina7,Roswarski Joseph13,Emanuel Michael8,Braylan Raul7,Turkbey Baris5,Choyke Peter5,Camphausen Kevin4,Stetler-Stevenson Maryalice6,Steinberg Seth M.9,Figg William D.10,Jones Jennifer46

Affiliation:

1. Multiple Myeloma Program, Lymphoid Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

2. Myeloma Program, Sylvester Comprehensive Cancer Center, University of Miami, Miami, Florida, USA

3. Hematology-Oncology Department, John P. Murtha Cancer Center, Walter Reed National Military Medical Center, Bethesda, Maryland, USA

4. Radiation Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

5. Molecular Imaging Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

6. Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

7. Hematology Service, Department of Laboratory Medicine, National Institutes of Health, Bethesda, Maryland, USA

8. Office Research Nursing, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

9. Biostatistics & Data Management Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

10. Molecular Pharmacology Section, Genitourinary Malignancies Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA

Abstract

Abstract Lessons Learned Despite the initial optimism for using immune checkpoint inhibition in the treatment of multiple myeloma, subsequent clinical studies have been disappointing. Preclinical studies have suggested that priming the immune system with various modalities in addition to checkpoint inhibition may overcome the relative T-cell exhaustion or senescence; however, in this small data set, radiotherapy with checkpoint inhibition did not appear to activate the antitumor immune response. Background Extramedullary disease (EMD) is recognized as an aggressive subentity of multiple myeloma (MM) with a need for novel therapeutic approaches. We therefore designed a proof-of-principle pilot study to evaluate the synergy between the combination of the anti–PD-L1, avelumab, and concomitant hypofractionated radiotherapy. Methods This was a single-arm phase II Simon two-stage single center study that was prematurely terminated because of the COVID-19 pandemic after enrolling four patients. Key eligibility included patients with relapsed/refractory multiple myeloma (RRMM) who had exhausted or were not candidates for standard therapy and had at least one lesion amenable to radiotherapy. Patients received avelumab until progression or intolerable toxicity and hypofractionated radiotherapy to a focal lesion in cycle 2. Radiotherapy was delayed until cycle 2 to allow the avelumab to reach a study state, given the important observation from previous studies that concomitant therapy is needed for the abscopal effect. Results At a median potential follow-up of 10.5 months, there were no objective responses, one minimal response, and two stable disease as best response. The median progression-free survival (PFS) was 5.3 months (95% confidence interval [CI]: 2.5–7.1 months), and no deaths occurred. There were no grade ≥3 and five grade 1–2 treatment-related adverse events. Conclusion Avelumab in combination with radiotherapy for patients with RRMM and EMD was associated with very modest systemic clinical benefit; however, patients did benefit as usual from local radiotherapy. Furthermore, the combination was very well tolerated compared with historical RRMM treatment regimens.

Publisher

Oxford University Press (OUP)

Subject

Cancer Research,Oncology

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