Neoadjuvant relatlimab and nivolumab in resectable melanoma
(1) Amaria RN (2) Postow M (3) Burton EM (4) Tezlaff MT (5) Ross MI (6) Torres-Cabala C (7) Glitza IC (8) Duan F (9) Milton DR (10) Busam K (11) Simpson L (12) McQuade JL (13) Wong MK (14) Gershenwald JE (15) Lee JE (16) Goepfert RP (17) Keung EZ (18) Fisher SB (19) Betof-Warner A (20) Shoushtari AN (21) Callahan M (22) Coit D (23) Bartlett EK (24) Bello D (25) Momtaz P (26) Nicholas C (27) Gu A (28) Zhang X (29) Korivi BR (30) Patnana M (31) Patel SP (32) Diab A (33) Lucci A (34) Prieto VG (35) Davies MA (36) Allison JP (37) Sharma P (38) Wargo JA (39) Ariyan C (40) Tawbi HA
(1) Amaria RN (2) Postow M (3) Burton EM (4) Tezlaff MT (5) Ross MI (6) Torres-Cabala C (7) Glitza IC (8) Duan F (9) Milton DR (10) Busam K (11) Simpson L (12) McQuade JL (13) Wong MK (14) Gershenwald JE (15) Lee JE (16) Goepfert RP (17) Keung EZ (18) Fisher SB (19) Betof-Warner A (20) Shoushtari AN (21) Callahan M (22) Coit D (23) Bartlett EK (24) Bello D (25) Momtaz P (26) Nicholas C (27) Gu A (28) Zhang X (29) Korivi BR (30) Patnana M (31) Patel SP (32) Diab A (33) Lucci A (34) Prieto VG (35) Davies MA (36) Allison JP (37) Sharma P (38) Wargo JA (39) Ariyan C (40) Tawbi HA
Relatlimab and nivolumab combination immunotherapy improves progression-free survival over nivolumab monotherapy in patients with unresectable advanced melanoma(1). We investigated this regimen in patients with resectable clinical stage III or oligometastatic stage IV melanoma (NCT02519322). Patients received two neoadjuvant doses (nivolumab 480_mg and relatlimab 160_mg intravenously every 4 weeks) followed by surgery, and then ten doses of adjuvant combination therapy. The primary end point was pathologic complete response (pCR) rate(2). The combination resulted in 57% pCR rate and 70% overall pathologic response rate among 30 patients treated. The radiographic response rate using Response Evaluation Criteria in Solid Tumors 1.1 was 57%. No grade 3-4 immune-related adverse events were observed in the neoadjuvant setting. The 1- and 2-year recurrence-free survival rate was 100% and 92% for patients with any pathologic response, compared to 88% and 55% for patients who did not have a pathologic response (P_=_0.005). Increased immune cell infiltration at baseline, and decrease in M2 macrophages during treatment, were associated with pathologic response. Our results indicate that neoadjuvant relatlimab and nivolumab induces a high pCR rate. Safety during neoadjuvant therapy is favourable compared to other combination immunotherapy regimens. These data, in combination with the results of the RELATIVITY-047 trial(1), provide further confirmation of the efficacy and safety of this new immunotherapy regimen.
Author Info:
(1) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. rnamaria@mdanderson.org. (2) Department of Medicine, Memorial Sloa
n Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. (3) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (4) Department of Pathology, The University of California San Francisco, San Francisco, CA, USA. (5) Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, US. (6) Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (7) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (8) Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (9) Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (10) Department of Pathology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (11) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (12) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (13) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (14) Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, US. (15) Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, US. (16) Department of Head and Neck Surgery, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (17) Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, US. (18) Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, US. (19) Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. (20) Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. (21) Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. (22) Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (23) Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (24) Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (25) Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY, USA. (26) Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (27) Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (28) Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (29) Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (30) Department of Radiology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (31) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (32) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (33) Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, US. (34) Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (35) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (36) Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (37) Department of Immunology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA. (38) Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, US. (39) Department of Surgical Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. (40) Department of Melanoma Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.
