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  • 1
    In: European Journal of Cancer, Elsevier BV, Vol. 75 ( 2017-04), p. 47-55
    Type of Medium: Online Resource
    ISSN: 0959-8049
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    Language: English
    Publisher: Elsevier BV
    Publication Date: 2017
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  • 2
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 7_suppl ( 2017-03-01), p. 147-147
    Abstract: 147 Background: We previously confirmed the feasibility of adoptive cell therapy (ACT) with tumor infiltrating lymphocytes (TIL) for patients with advanced melanoma. Patients successfully treated had a 38% response rate, but patient attrition due to progression before ACT (21%) resulted in a response rate of only 26% based on intent to treat (IIT) analysis. We hypothesized that combination immunotherapy would decrease attrition due to progression. Here we present the final report of a pilot trial combining ipilimumab (IPI) and ACT. Methods: Thirteen patients with metastatic melanoma were accrued to an IRB-approved trial. All had 〉 1 cm 3 of soft tissue/nodal metastases amenable to resection leaving residual disease. Patients received 3 mg/kg of IPI two weeks prior to tumor resection for TIL generation. One week following resection, a second dose of IPI was administered. ACT included pre-conditioning chemotherapy and TIL infusion followed by IL-2. Two additional doses of IPI were given 2 and 5 weeks after ACT. Feasibility was a primary endpoint and considered achieved if ≥ 2 doses of IPI and TIL were infused to at least 60% of all patients. The clinical responses were assessed by RECIST 1.1 criteria at 12 weeks following TIL transfer. Results: All patients received at least 2 doses of IPI, and 12 of the 13 patients (92%) received TIL. One patient (7%) dropped out due to progression before TIL infusion. TIL were expanded from 47.2% of tumor fragments and 58.7% of these fragments generated TIL reactive to autologous tumor. Median number of infused TIL was 6.5e10 (2.29e10-1.04e11) and median 85% were CD8+ (27-99). At 12 weeks following infusion, of the 13 patients enrolled, there were 6 responders (46%). Median progression-free survival was 7.4 months (1.4-42.2). Grade ≥3 immune-related adverse events included colitis (1), uveitis (1), and hypothyroidism (1). Conclusions: IPI combined with ACT with TILs for patients with advanced melanoma is feasible with decreased attrition due to progression and is associated with promising clinical results based upon ITT analysis. This combination approach of TIL cell therapy and co-inhibitory blockade serves as a model for future efforts to improve the efficacy of immunotherapy for patients with cancer. Clinical trial information: NCT01701674.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
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  • 3
    Online Resource
    Online Resource
    American Society of Clinical Oncology (ASCO) ; 2017
    In:  Journal of Clinical Oncology Vol. 35, No. 15_suppl ( 2017-05-20), p. 9584-9584
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 35, No. 15_suppl ( 2017-05-20), p. 9584-9584
    Abstract: 9584 Background: While BRAF and MEK inhibitors are approved for patients with BRAF V600 + unresectable/metastatic melanoma, their role in the neoadjuvant setting is less well defined. Results from small trials have noted robust response rates, but less is known about histological patterns of response in resected tumor specimens and relation to outcome in these patients (pts). Methods: In a retrospective study, we analyzed the clinical and pathologic patterns of response to neoadjuvant BRAF ± MEK inhibitor therapy in pts with locally advanced melanoma subsequently rendered disease free with surgery. Results: Twenty pts were identified, nine with stage IIIC and 11 with stage IV melanoma. Seven patients received neoadjuvant vemurafenib (VEM), 12 received dabrafenib + trametinib (D+T), and one encorafenib + binimetinib. The median duration of treatment was 7.8 months. Seven patients (35%) had a pathologic complete response (pCR); six of them had received combination therapy, 5 with D+T, 1 VEM with an HSP90 inhibitor. Four distinct histologic patterns were observed in the resected tumor specimens: necrotic, fibrotic/melanotic (tumoral melanosis), hyalinized, or mixed. With median follow-up of 25 months (range 1-60), six pts (30%) had experienced recurrence; three developed CNS metastases. Four of the six patients had received neoadjuvant D+T; three were restarted on their prior targeted therapy at recurrence and all responded. All 6 pts with recurrence had residual disease in the surgical specimen; three had no necrosis identified. In contrast to the 13 pts with persistent tumor, none of the 7 pCR pts has relapsed (p = 0.05). There was a trend towards improved relapse-free-survival (RFS) with a pCR, with a 1 yr of RFS-rate of 50.4% vs 100% in pCR.(p = 0.08) Of the 14 patients without subsequent recurrence, 9 had either a pure necrotic histology, or a mixed histological pattern that included necrosis. Conclusions: In locally advanced or M1a BRAF mutant melanoma, attaining a pCR to neoadjuvant targeted therapy may correlate with improved patient outcomes and be more likely achieved with combination therapy. Presence of necrosis in the surgical specimen appears be a favorable prognostic factor.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2017
    detail.hit.zdb_id: 2005181-5
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  • 4
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 15_suppl ( 2019-05-20), p. 9590-9590
    Abstract: 9590 Background: Until recently, most patients (pts) with SLN+ MEL underwent CLND, a procedure mandated in published trials of adjuvant anti-PD-1 therapy to date. Following MSLT-II, this practice has dramatically changed with most pts now undergoing surveillance or adjuvant therapy without CLND. In addition, pts with in-transit/satellite MEL were excluded or not reported in these prior adjuvant studies. Our aim was to explore real-world outcomes of adjuvant NIVO in these pts. Methods: We carried out a single center retrospective analysis of stage 3 MEL pts who received adjuvant NIVO. Results: 32 pts with SLN+ MEL who did not undergo a CLND and started adjuvant NIVO within 3 months of surgery were included. Median age was 60 (26-77); per AJCC v7, 12 pts had Stage 3A, 11 stage 3B, and 9 pts had Stage 3C MEL. One was acral MEL; 18 had an ulcerated primary. 6 pts had BRAF-mutant MEL, 20 had BRAF-WT, and 6 unknown. NIVO treatment was 240 mg Q2wks or 480 mg Q4wks, up to one year. 21 pts developed grade 1/2 immune-related adverse events (irAEs), and 1 pt stopped NIVO due to toxicity (fatigue). With median follow-up of 7 months, only 1 pt had a recurrence, which was in the in SLN+ nodal basin; pt was rendered disease-free with surgery. The relapse-free rate (RFS) rate at 1 year was 95% (95% CI, 71-100). Of 21 pts with in-transit/satellite recurrent MEL (median age 68 [29-84]) who started adjuvant NIVO (no prior drug treatment), 5 had BRAF-mutant MEL, 14 BRAF-WT, 2 unknown; two were acral-lentiginous. 3 pts had recurrences: 2 regional and 1 distant mets, treated with surgery, TVEC, or BRAF-targeted therapy. Median follow-up was 8 months from NIVO start; 1-year RFS was 72% (95% CI 32-91). 15 pts developed irAEs; in 12, these were grade 1-2 and in 3, were grade 3 that led to discontinuation. Conclusions: While preliminary, these findings suggest that adjuvant anti-PD-1 therapy may be effective in SLN+ pts who forego CLND prior to adjuvant treatment, as 1-year RFS rate appears similar to rates in the published adjuvant anti-PD-1 trials that mandated CLND. This therapy may be similarly effective in pts with resected in-transit/satellite stage 3 melanoma. Further follow-up will be presented.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
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    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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