Discordant response comparing 18F-FDG PET/CT with response assessment by RECIST in patients with advanced melanoma treated with immune checkpoint blockade.

10046 Background: Immune checkpoint blockade (ICB) has changed the natural history advanced melanoma (AM). Based on phase III trial, which used RECIST criteria, the complete response (CR) rate with anti-PD1 therapy is around 20%. In daily practice, PET/CT is a useful tool to evaluate response to treatment in melanoma patients. Little is known about the number of patients who achieve metabolic CR by PET/CT but with anatomic residual disease and their prognosis. Methods: We conducted a retrospective analysis of patients with AM treated with ICB who achieved metabolic CR by PET/CT but with residual disease on tomography and compared to patients with RECIST CR in a high-volume cancer center. Progression-free (PFS) and overall survival (OS) were obtained by Kaplan Meier method and log-rank test. Results: One hundred seventy pts with AM treated with anti-PD1 (79%) or anti-PD1 + anti- CTLA4 (21%) betweenSeptember 2013 and December 2019 were analyzed. At a median follow-up of 23.6 months, seventy-five (44%) pts achieved CR. RECIST criteria: 22 pts (29.3%) and metabolic CR: 53 pts (70.7%). All patients with metabolic CR had RECIST partial response. The median total time on treatment was 14.8m (95%CI:0.9-42.3). The median time to reach CR was 5.4m (95%CI: 3-39). The median time of treatment after CR was 6.8m (95%CI: 0-21.4). The rate of CR patients off treatment at the moment of this analysis was 69%. The median follow-up after discontinuing treatment was 5.2m. There was no difference in PFS (36 month-rate: 84.4% vs 74%, p:0.64) and OS (36 month-rate: 100% vs 86.3%, p:0.14) between pts with CR based on RECIST or PET-CT, respectively. Median time for PFS and OS have not been reached until the date cut-off. Nine pts have relapsed (12%). Seven of them had residual disease on tomography but with no metabolic active lesion(s) at the time of the end of treatment. Conclusions: Twice more patients achieve complete response considering only metabolic parameters on PET/CT compared to RECIST criteria and they seem to have comparable prognosis.

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Clinical benefit and toxicity of nivolumab plus ipilimumab in patients with advanced melanoma previously treated with checkpoint blockade inhibitors.

Journal of Clinical Oncology ◽

10.1200/jco.2017.35.7_suppl.100 ◽

2017 ◽

Vol 35 (7_suppl) ◽

pp. 100-100

Author(s):

Claire Frances Friedman ◽

Jedd D. Wolchok ◽

Michael Andrew Postow ◽

Alexander Noor Shoushtari ◽

Margaret K. Callahan ◽

...

Keyword(s):

Treatment Failure ◽

Median Time ◽

Systemic Treatment ◽

Immune Therapy ◽

Progression Free Survival ◽

Advanced Melanoma ◽

Checkpoint Blockade ◽

Systemic Treatments ◽

Previously Treated

100 Background: The combination of nivolumab and ipilimumab (nivo+ipi) prolongs progression-free survival in treatment-naïve patients (pts) with advanced melanoma. However, the efficacy and tolerability of nivo+ipi in pts previously treated with checkpoint blockade inhibitors (CPI) are unknown. Methods: 19 pts previously treated with CPI (ipi or anti-PD-1 as single agents) were treated with nivo+ipi at MSKCC. Ipi (3mg/kg) and nivo (1mg/kg) were administered q3 weeks for 4 doses with the option to continue anti-PD1 maintenance. Pts were followed for time to treatment failure (TTF), defined as the time from the date of first nivo+ipi infusion to the date of one of the following: clinical progression, new locally-directed treatment (ie surgery or radiotherapy), new systemic treatment other than anti-PD-1 monotherapy, or death. Results: 15 pts (79%) had stage M1c disease and 12 (63%) had a cutaneous primary. Pts had received a median of 2 prior systemic treatments (range 1-7). 10 pts (53%) had received prior ipi and 17 pts (89%) had received prior anti-PD-1 treatment; 8 pts (42%) had received both. The median time between anti-PD-1 monotherapy and nivo+ipi was 51 days (range 20-385). Pts received a median of 3 doses of combination therapy; 9 of 19 pts (47%) received all 4 doses. With a median follow-up time of 210 days, 8 pts (42.1%) remained on combination immune therapy, 9 pts (47%) switched systemic treatments or had a local procedure and 6 pts (31.6%) died. Median time on immunotherapy for those still alive and without treatment failure was 105 days (range 26-343). The median TTF was 78 days (range 42-220). The most common systemic treatment after nivo+ipi failure was BRAF-targeted therapy (5/9 or 56.3%). The median number of immune related adverse events (irAEs) was 1 (range 0-3). Rash (26%), Hepatitis (16%) and Colitis (16%) were the most common irAEs. Conclusions: With a short median follow-up, administration of nivo+ipi in CPI-experienced patients with advanced melanoma was associated with a short TTF. 58% of patients died or had treatment failure within the follow-up period. More research is needed to guide the utilization of combination immunotherapy in this setting.

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Combination immune checkpoint blockade with ipilimumab and nivolumab in the management of advanced melanoma

Expert Opinion on Biological Therapy ◽

10.1517/14712598.2016.1141195 ◽

2016 ◽

Vol 16 (3) ◽

pp. 389-396 ◽

Cited By ~ 22

Author(s):

Lavinia Spain ◽

James Larkin

Keyword(s):

Immune Checkpoint ◽

Immune Checkpoint Blockade ◽

Advanced Melanoma ◽

Checkpoint Blockade

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Acute neurologic toxicity of palliative radiotherapy for brain metastases in patients receiving immune checkpoint blockade

Neuro-Oncology Practice ◽

10.1093/nop/npy042 ◽

2018 ◽

Vol 6 (4) ◽

pp. 297-304 ◽

Cited By ~ 4

Author(s):

W Tristram Arscott ◽

Simeng Zhu ◽

John P Plastaras ◽

Amit Maity ◽

Michelle Alonso-Basanta ◽

...

Keyword(s):

Brain Metastases ◽

Immune Checkpoint ◽

Performance Status ◽

Single Agent ◽

Whole Brain Radiotherapy ◽

Nonsmall Cell Lung Cancer ◽

Immune Checkpoint Blockade ◽

Checkpoint Blockade ◽

Acute Neurotoxicity

Abstract Background The interaction between immune checkpoint blockade (ICB) and radiation (RT) for brain metastases has not been well understood. Given that acute neurotoxicity from this combination is not well characterized, we reviewed patients receiving ICB and RT for brain metastases. Methods Patients treated with ICB and cranial RT from 2010 through 2017 were reviewed. ICB and RT must have been administered within 30 days of each other. Treatment parameters, performance status, symptoms prior to treatment, and toxicity were extracted from the electronic medical record. Survival was calculated from the end of RT to last follow-up or death. Results Seventy-eight patients were included. Median follow-up was 177 days (range, 12-1603). Median age was 64 years old (range, 29-98) and 47 (63%) were male. The main tumor types were melanoma (n = 47) and nonsmall-cell lung cancer (n = 19). Fifty-seven patients were treated with stereotactic radiosurgery (SRS) and 21 with whole-brain radiotherapy (WBRT). Most patients received single-agent ICB, though 4 patients received nivolumab and ipilimumab. Forty-one (53%) patients reported no neurologic toxicity. Grade 2 or greater neurologic toxicities were reported in 12 (21%) and 8 (38%) patients in the SRS and WBRT groups, respectively. WBRT was associated with a greater risk of any neurotoxicity, though there was no correlation between ICB agent and toxicity. Sequencing of ICB and RT (ie, <30 days vs <7) did not influence rates of toxicity. Conclusions ICB during SRS or WBRT does not appear to worsen acute neurotoxicity compared to historical controls of RT alone.

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Generalization and representativeness of phase III immune checkpoint blockade trials in non‐small cell lung cancer

Thoracic Cancer ◽

10.1111/1759-7714.12641 ◽

2018 ◽

Vol 9 (6) ◽

pp. 736-744 ◽

Cited By ~ 7

Author(s):

Shin Hye Yoo ◽

Bhumsuk Keam ◽

Miso Kim ◽

Tae Min Kim ◽

Dong‐Wan Kim ◽

...

Keyword(s):

Lung Cancer ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Immune Checkpoint ◽

Immune Checkpoint Blockade ◽

Small Cell ◽

Checkpoint Blockade ◽

Phase Iii ◽

Small Cell Lung

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Updated phase 1 results of teclistamab, a B-cell maturation antigen (BCMA) × CD3 bispecific antibody, in relapsed/refractory multiple myeloma (MM).

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.8007 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. 8007-8007

Author(s):

Amrita Y. Krishnan ◽

Alfred L. Garfall ◽

Maria-Victoria Mateos ◽

Niels W.C.J. van de Donk ◽

Hareth Nahi ◽

...

Keyword(s):

Median Time ◽

T Cell Activation ◽

Cell Activation ◽

Residual Disease ◽

Phase 1 ◽

Complete Response ◽

Low Grade ◽

Exposure Profile ◽

Grade 3

8007 Background: BCMA-targeted immunotherapies offer considerable promise for relapsed/refractory MM. Teclistamab (JNJ-64007957) is a BCMA × CD3 bispecific IgG4 antibody that redirects CD3+ T cells to BCMA-expressing MM cells. We present updated results of patients (pts) treated at the recommended phase 2 dose (RP2D) in the first-in-human phase 1 study of teclistamab. Methods: Eligible pts had MM and were relapsed, refractory or intolerant to established therapies. Primary objectives were to identify the RP2D (part 1) and characterize safety and tolerability of teclistamab at the RP2D (part 2). Teclistamab was given intravenously (IV; range 0.3–19.2 µg/kg [biweekly]; range 19.2–720 µg/kg [weekly]) or subcutaneously (SC; range 80.0–3000 µg/kg weekly) in different cohorts, with step-up dosing used for ≥38.4 µg/kg doses. Adverse events (AEs) were graded by CTCAE v4.03 (cytokine release syndrome [CRS] by Lee et al 2014). Response was assessed per IMWG criteria. Results: As of Feb 4, 2021, 156 pts received teclistamab (IV n = 84; SC n = 72). The RP2D, identified as weekly SC 1500 µg/kg teclistamab with 60.0 and 300 µg/kg step-up doses, was given to 40 pts (median follow-up 4.3 mo [range 1.1–10.4+]). Pts dosed at the RP2D (median age, 62.5 y [range, 39–84]; 65% male) had received a median of 5 prior lines of therapy (range 2–11; 100% triple-class exposed; 65% penta-drug exposed; 83% triple-class refractory; 35% penta-drug refractory; 85% refractory to their last line of therapy). There were no dose-limiting toxicities at the RP2D in part 1. The most common AEs at the RP2D were CRS (70%; grade 3/4 0) and neutropenia (60%; grade 3/4 40%); grade 1 neurotoxicity was reported in 1 (3%) pt. Median time to CRS onset was later with SC vs IV dosing (day after SC injection vs day of IV infusion). The overall response rate in response-evaluable pts treated at the RP2D (n = 40) was 65%; 58% achieved a very good partial response or better and 30% achieved a complete response (CR) or better; median time to first confirmed response was 1.0 mo (range 0.2–3.1). At the RP2D, median duration of response was not reached; 23 of 26 responders (88%), after median follow-up of 5.3 mo (range 1.2–10.4+), were alive and continuing on treatment with responses deepening over time. Of 14 evaluable pts across all cohorts, 9 with CR were minimal residual disease–negative at 10-6. At the RP2D, teclistamab exposure was sustained across the dosing interval and exceeded target levels, and consistent T cell activation was observed. Conclusions: Teclistamab at the RP2D (weekly 1500 µg/kg SC) was well-tolerated and showed encouraging efficacy with durable, deepening responses, supporting further investigation as monotherapy and in combination with other agents. With the extended exposure profile at the RP2D and delayed and low-grade CRS observed with SC administration, alternative SC dosing strategies are being explored. Clinical trial information: NCT03145181.

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