Nilotinib is a rationally designed 2nd-generation bcr-abl inhibitor. It is ∼30-fold more potent t... more Nilotinib is a rationally designed 2nd-generation bcr-abl inhibitor. It is ∼30-fold more potent than imatinib against wild-type bcr-abl and active against 32/33 imatinib-resistant bcr-abl mutants in preclinical models. In an open-label phase II study of nilotinib in imatinib-resistant or -intolerant CML-CP patients (pts), we assessed the occurrence of mutations and the efficacy stratified by BCR-ABL mutational status. Prior to therapy, 35 mutations affecting 28 amino acids in the BCR-ABL kinase domain were identified by direct sequencing in 39% (106/270) of the pts analyzed. The incidence of baseline mutation was higher in imatinib-resistant (100/183, 55%) versus imatinib-intolerant pts (6/86, 7%). After 12 months of therapy, complete hematologic response (CHR) was achieved in 85%, major cytogenetic response (MCR) in 60%, and complete cytogenetic response (CCR) in 45% of pts without baseline mutations versus 67, 49 and 29% of pts with mutations. Among patients with baseline mutations, responses were observed broadly in all genotypes identified, but rates of responses differed by the in vitro sensitivity of the mutant clone against nilotinib. Pts with sensitive mutations of ≤100 nM cellular IC50 had the best response rate and were comparable to pts without baseline mutations. Pts with less sensitive mutations (IC50 201–800nM:Y253H, E255K, E255V, F359C) had responses but the response rate were lower then those of the two other groups (IC50 101–200nM and 201–800nM). The nilotinib-resistant T315I mutation (IC50>800nM) was identified at baseline in 5 cases (one pt had a limited response followed by progression). The less sensitive mutations (IC50 201–800nM) and the T315I mutation occurred in 8% and 2% of all pts assessed for baseline mutations, respectively. With a median follow up of 12 months, progression occurred in 15% (25/164) versus 40% (42/106) of pts without and with baseline mutations. Nine of 18 with less sensitive baseline mutations and 3 of 5 with T315I progressed, but the baseline mutation most frequently associated with progression was F359V (7/9). In 67 cases of progression, mutational data at or within 3 months of progression were available in 28 cases. Among the 28 pts, 7 (25%) had no mutation; 9 (32%) had the same baseline mutation (including F359V in 3; Y253F/H in 3; E255K in 1; and T315I in 1). A further 12 (43%) pts showed new emerging mutations at progression, 4 with T315I, 4 E255K, 3 Y253H, and 1 F359C. The other 7 pts with emerging mutations had not progressed. In total 21 pts were found with emerging mutations, 19 (90%) had a different mutation at baseline. In summary, nilotinib responses were observed across a variety of BCR-ABL mutations. Preliminary data suggest that mutational status at baseline and/or the emergence of new mutations may influence disease progression. Less sensitive or resistant mutations represented 10% of the pt population and may be associated with less favorable responses. Longer follow up is required.
Supplementary Methods and Supplementary Table 1. The supplementary data file contains the supplem... more Supplementary Methods and Supplementary Table 1. The supplementary data file contains the supplemental methods section describing the source of the patient samples used in the initial validation of the five-gene signature assay and supplementary table 1 which lists the number of patients with MB with tumor samples assessed per the five-gene signature assay from each clinical study as a second validation set.
Background: Follicular lymphoma (FL) is a heterogeneous disease, and clinical presentation is hig... more Background: Follicular lymphoma (FL) is a heterogeneous disease, and clinical presentation is highly variable. The Follicular Lymphoma International Prognostic Index (FLIPI-2) identifies prognostic factors at diagnosis, but does not predict in whom and when to initiate first-line therapy (1LT) (Federico 2009). Recommended therapies for 1LT vary by stage, symptomatology, and tumor burden, but include monotherapy with rituximab (R) or in combination with other chemotherapies. Survival of FL patients in the R era has greatly improved, but few studies have evaluated survival outcomes in patients seen in routine clinical care. This study aimed to evaluate survival outcomes in a United States (US) population of newly diagnosed FL patients seen in routine clinical care. Methods: A retrospective study was conducted in which the presence of ≥1 inpatient record or ≥2 outpatient records with FL diagnosis codes were used to identified newly diagnosed FL patients from Humedica, a large US electronic medical record database, between 01/01/08 and 07/31/15. The study index date was the first FL record. Patients who subsequently initiated 1LT with bendamustine+R or other R-based combinations were followed from the date of treatment initiation until death, loss to follow-up, or end of study (09/30/15) for the evaluation of the survival outcomes. Median progression-free survival (PFS) (defined as initiation of second-line therapy, evidence of supportive care >30 days after the end of a line of therapy, or death), median overall survival (OS), and PFS and OS rates at 2 years following initiation of 1LT were evaluated using Kaplan-Meier analyses. Cox proportional hazard models were used to further assess the impact of bendamustine+R and other R-based combinations on OS and PFS at 2 years. Results: 1,346 newly diagnosed FL patients who initiated 1LT met the patient selection criteria; of these, 362 and 417 received bendamustine+R and other R-based combinations, respectively. The majority of the other R-based combinations were R-CHOP (48.7%) and R-CVP (25.4%). The mean age (bendamustine+R, 65.3 [SD: 11.5] and other R-based combinations, 65.0 [SD: 11.6]) and proportion of males (bendamustine+R, 48.9% and R-based combinations, 48.0%) were similar between the two treatment groups. At baseline, 19.3% of patients treated with bendamustine+R and 15.3% of patients treated with other R-based combinations had a Charlson Comorbidity Index of ≥2. Unadjusted Kaplan-Meier analysis revealed that for patients treated with bendamustine+R and R-based combinations, 2-year OS rates were 90.2% and 86.2% (P=0.0916), respectively, and 2-year PFS rates were 76.7% and 56.0% (P Conclusion: In routine clinical practice, patients treated with bendamustine+R in 1LT had significantly better 2-year PFS than patients treated with other R-based combination therapy, while OS was similar between the groups. These results are similar to that of the clinical trial comparing bendamustine plus rituximab and R-CHOP, where PFS was found to be significantly better with bendamustine plus rituximab and OS was similar (Rummel 2009). Disclosures Galaznik: Takeda Pharmaceuticals: Employment, Equity Ownership. Bell: Takeda Pharmaceuticals: Employment, Equity Ownership. Hamilton: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy; Xcenda: Employment. Ogbonnaya: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy; Xcenda: Employment. Hennenfent: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy; Xcenda: Employment. Eaddy: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy; Xcenda: Employment. Shou: Takeda Pharmaceuticals: Employment, Equity Ownership.
Megakaryocytes are rare hematopoietic cells comprising only about 0.02-0.05% of the bone marrow n... more Megakaryocytes are rare hematopoietic cells comprising only about 0.02-0.05% of the bone marrow nucleated cell population. Because of the relative infrequency of megakaryocytes in the bone marrow and their fragility in vitro, studies to characterize expression of platelet-specific genes have mostly been carried out in continuous cell lines originating from leukaemic marrow or blood cells that express a range of megakaryocytic phenotypic properties. HEL cells, which are representative of such cell lines, were instrumental in getting the molecular analysis of megakaryocytes and platelets established, and although these cells are still useful for many studies, it has become clear that they have significant limitations. These limitations include the fact that these lines only approximate megakaryocytes. These lines do not contain α-granules, do not demarcate or release platelets, respond appropriately to thrombopoietin (TPO), or express the high levels of such platelet-specific proteins such as the integrin αIIb and platelet factor 4 (PF4). Other proteins such as the platelet-restricted G protein G(z)α has not been detected in any of these cell lines. Further, these cell lines often express a mixture of multiple different lineages and can be easily shifted from one lineage to another.
6516 Background: BCR-ABL transcript levels have been reported to be a predictor of response outco... more 6516 Background: BCR-ABL transcript levels have been reported to be a predictor of response outcomes, including the detection of new mutations, in pts with imatinib resistance. In this posthoc anal...
6513 Background: Response dynamics in pts treated with nilotinib for imatinib failure may be diff... more 6513 Background: Response dynamics in pts treated with nilotinib for imatinib failure may be different than imatinib in front line. Many pts treated with nilotinib in the second line achieved cytogenetic responses early (median time to MCyR and CCyR of 2.8 mo and 3.3 mo). A previous landmark analysis demonstrated BCR-ABL% (IS) at 3 months (mo) on nilotinib predicted achievement of subsequent cytogenetic response. Here, we investigated whether early molecular response before 3 mo was associated with subsequent cytogenetic response. Methods: CML-CP pts (N = 321) with imatinib resistance or intolerance were grouped by 1 mo BCR-ABL% (IS) and landmark analyses were performed to evaluate probability of cytogenetic response with a minimum follow-up of 24 mo. Results: Early molecular response of BCR-ABL% (IS) ≤ 10 occurred in 19% of pts who received nilotinib. Pts with BCR-ABL% (IS) >1 – ≤10 (n = 37) had higher probability of MCyR by 12 mo (84%) compared with pts with BCR-ABL% (IS) >10 (55%) (n = 202). Pts with B...
BACKGROUND Intravenous TTI-621 (SIRPα-IgG1 Fc) was previously shown to have activity in relapsed ... more BACKGROUND Intravenous TTI-621 (SIRPα-IgG1 Fc) was previously shown to have activity in relapsed or refractory haematological malignancies. This phase 1 study evaluated the safety and activity of TTI-621 in patients with percutaneously accessible relapsed or refractory mycosis fungoides, Sézary syndrome, or solid tumours. Here we report the clinical and translational results among patients with mycosis fungoides or Sézary syndrome. METHODS This multicentre, open-label, phase 1 study was conducted at five academic health-care and research centres in the USA. Eligible patients were aged 18 years or older; had injectable, histologically or cytologically confirmed relapsed or refractory cutaneous T-cell lymphoma (CTCL) or solid tumours; Eastern Cooperative Oncology Group performance status of 2 or less; and adequate haematological, renal, hepatic, and cardiac function. TTI-621 was injected intralesionally in a sequential dose escalation (cohorts 1-5; single 1 mg, 3 mg, or 10 mg injection or three 10 mg injections weekly for 1 or 2 weeks) and in expansion cohorts (cohorts 6-9; 2 week induction at the maximum tolerated dose; weekly continuation was allowed). In cohort 6, patients were injected with TTI-621 in a single lesion and in cohort 7, they were injected in multiple lesions. In cohort 8, TTI-621 was combined with pembrolizumab 200 mg injections per product labels. In cohort 9, TTI-621 was combined with the standard labelled dose of subcutaneous pegylated interferon alpha-2a 90 μg. The primary endpoint was the incidence and severity of adverse events. The study is registered with ClinicalTrials.gov, NCT02890368, and was closed by the sponsor to focus on intravenous studies with TTI-621. FINDINGS Between Jan 30, 2017, and March 31, 2020, 66 patients with mycosis fungoides, Sézary syndrome, other CTCL, or solid tumours were screened, 35 of whom with mycosis fungoides or Sézary syndrome were enrolled and received intralesional TTI-621 (escalation, n=13; expansion, n=22). No dose-limiting toxicities occurred; the maximum tolerated dose was not established. In the dose expansion cohorts, the maximally assessed regimen (10 mg thrice weekly for 2 weeks) was used. 25 (71%) patients had treatment-related adverse events; the most common (occurring in ≥10% of patients) were chills (in ten [29%] patients), injection site pain (nine [26%]), and fatigue (eight [23%]). No treatment-related adverse events were grade 3 or more or serious. There were no treatment-related deaths. Rapid responses (median 45 days, IQR 17-66) occurred independently of disease stage or injection frequency. 26 (90%) of 29 evaluable patients had decreased Composite Assessment of Index Lesion Severity (CAILS) scores; ten (34%) had a decrease in CAILS score of 50% or more (CAILS response). CAILS score reductions occurred in adjacent non-injected lesions in eight (80%) of ten patients with paired assessments and in distal non-injected lesions in one additional patient. INTERPRETATION Intralesional TTI-621 was well tolerated and had activity in adjacent or distal non-injected lesions in patients with relapsed or refractory mycosis fungoides or Sézary syndrome, suggesting it has systemic and locoregional abscopal effects and potential as an immunotherapy for these conditions. FUNDING Trillium Therapeutics.
Nilotinib is a rationally designed 2nd-generation bcr-abl inhibitor. It is ∼30-fold more potent t... more Nilotinib is a rationally designed 2nd-generation bcr-abl inhibitor. It is ∼30-fold more potent than imatinib against wild-type bcr-abl and active against 32/33 imatinib-resistant bcr-abl mutants in preclinical models. In an open-label phase II study of nilotinib in imatinib-resistant or -intolerant CML-CP patients (pts), we assessed the occurrence of mutations and the efficacy stratified by BCR-ABL mutational status. Prior to therapy, 35 mutations affecting 28 amino acids in the BCR-ABL kinase domain were identified by direct sequencing in 39% (106/270) of the pts analyzed. The incidence of baseline mutation was higher in imatinib-resistant (100/183, 55%) versus imatinib-intolerant pts (6/86, 7%). After 12 months of therapy, complete hematologic response (CHR) was achieved in 85%, major cytogenetic response (MCR) in 60%, and complete cytogenetic response (CCR) in 45% of pts without baseline mutations versus 67, 49 and 29% of pts with mutations. Among patients with baseline mutations, responses were observed broadly in all genotypes identified, but rates of responses differed by the in vitro sensitivity of the mutant clone against nilotinib. Pts with sensitive mutations of ≤100 nM cellular IC50 had the best response rate and were comparable to pts without baseline mutations. Pts with less sensitive mutations (IC50 201–800nM:Y253H, E255K, E255V, F359C) had responses but the response rate were lower then those of the two other groups (IC50 101–200nM and 201–800nM). The nilotinib-resistant T315I mutation (IC50>800nM) was identified at baseline in 5 cases (one pt had a limited response followed by progression). The less sensitive mutations (IC50 201–800nM) and the T315I mutation occurred in 8% and 2% of all pts assessed for baseline mutations, respectively. With a median follow up of 12 months, progression occurred in 15% (25/164) versus 40% (42/106) of pts without and with baseline mutations. Nine of 18 with less sensitive baseline mutations and 3 of 5 with T315I progressed, but the baseline mutation most frequently associated with progression was F359V (7/9). In 67 cases of progression, mutational data at or within 3 months of progression were available in 28 cases. Among the 28 pts, 7 (25%) had no mutation; 9 (32%) had the same baseline mutation (including F359V in 3; Y253F/H in 3; E255K in 1; and T315I in 1). A further 12 (43%) pts showed new emerging mutations at progression, 4 with T315I, 4 E255K, 3 Y253H, and 1 F359C. The other 7 pts with emerging mutations had not progressed. In total 21 pts were found with emerging mutations, 19 (90%) had a different mutation at baseline. In summary, nilotinib responses were observed across a variety of BCR-ABL mutations. Preliminary data suggest that mutational status at baseline and/or the emergence of new mutations may influence disease progression. Less sensitive or resistant mutations represented 10% of the pt population and may be associated with less favorable responses. Longer follow up is required.
Supplementary Methods and Supplementary Table 1. The supplementary data file contains the supplem... more Supplementary Methods and Supplementary Table 1. The supplementary data file contains the supplemental methods section describing the source of the patient samples used in the initial validation of the five-gene signature assay and supplementary table 1 which lists the number of patients with MB with tumor samples assessed per the five-gene signature assay from each clinical study as a second validation set.
Background: Follicular lymphoma (FL) is a heterogeneous disease, and clinical presentation is hig... more Background: Follicular lymphoma (FL) is a heterogeneous disease, and clinical presentation is highly variable. The Follicular Lymphoma International Prognostic Index (FLIPI-2) identifies prognostic factors at diagnosis, but does not predict in whom and when to initiate first-line therapy (1LT) (Federico 2009). Recommended therapies for 1LT vary by stage, symptomatology, and tumor burden, but include monotherapy with rituximab (R) or in combination with other chemotherapies. Survival of FL patients in the R era has greatly improved, but few studies have evaluated survival outcomes in patients seen in routine clinical care. This study aimed to evaluate survival outcomes in a United States (US) population of newly diagnosed FL patients seen in routine clinical care. Methods: A retrospective study was conducted in which the presence of ≥1 inpatient record or ≥2 outpatient records with FL diagnosis codes were used to identified newly diagnosed FL patients from Humedica, a large US electronic medical record database, between 01/01/08 and 07/31/15. The study index date was the first FL record. Patients who subsequently initiated 1LT with bendamustine+R or other R-based combinations were followed from the date of treatment initiation until death, loss to follow-up, or end of study (09/30/15) for the evaluation of the survival outcomes. Median progression-free survival (PFS) (defined as initiation of second-line therapy, evidence of supportive care >30 days after the end of a line of therapy, or death), median overall survival (OS), and PFS and OS rates at 2 years following initiation of 1LT were evaluated using Kaplan-Meier analyses. Cox proportional hazard models were used to further assess the impact of bendamustine+R and other R-based combinations on OS and PFS at 2 years. Results: 1,346 newly diagnosed FL patients who initiated 1LT met the patient selection criteria; of these, 362 and 417 received bendamustine+R and other R-based combinations, respectively. The majority of the other R-based combinations were R-CHOP (48.7%) and R-CVP (25.4%). The mean age (bendamustine+R, 65.3 [SD: 11.5] and other R-based combinations, 65.0 [SD: 11.6]) and proportion of males (bendamustine+R, 48.9% and R-based combinations, 48.0%) were similar between the two treatment groups. At baseline, 19.3% of patients treated with bendamustine+R and 15.3% of patients treated with other R-based combinations had a Charlson Comorbidity Index of ≥2. Unadjusted Kaplan-Meier analysis revealed that for patients treated with bendamustine+R and R-based combinations, 2-year OS rates were 90.2% and 86.2% (P=0.0916), respectively, and 2-year PFS rates were 76.7% and 56.0% (P Conclusion: In routine clinical practice, patients treated with bendamustine+R in 1LT had significantly better 2-year PFS than patients treated with other R-based combination therapy, while OS was similar between the groups. These results are similar to that of the clinical trial comparing bendamustine plus rituximab and R-CHOP, where PFS was found to be significantly better with bendamustine plus rituximab and OS was similar (Rummel 2009). Disclosures Galaznik: Takeda Pharmaceuticals: Employment, Equity Ownership. Bell: Takeda Pharmaceuticals: Employment, Equity Ownership. Hamilton: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy; Xcenda: Employment. Ogbonnaya: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy; Xcenda: Employment. Hennenfent: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy; Xcenda: Employment. Eaddy: Millennium Pharmaceuticals, Inc., a wholly owned subsidiary of Takeda Pharmaceutical Company Limited: Consultancy; Xcenda: Employment. Shou: Takeda Pharmaceuticals: Employment, Equity Ownership.
Megakaryocytes are rare hematopoietic cells comprising only about 0.02-0.05% of the bone marrow n... more Megakaryocytes are rare hematopoietic cells comprising only about 0.02-0.05% of the bone marrow nucleated cell population. Because of the relative infrequency of megakaryocytes in the bone marrow and their fragility in vitro, studies to characterize expression of platelet-specific genes have mostly been carried out in continuous cell lines originating from leukaemic marrow or blood cells that express a range of megakaryocytic phenotypic properties. HEL cells, which are representative of such cell lines, were instrumental in getting the molecular analysis of megakaryocytes and platelets established, and although these cells are still useful for many studies, it has become clear that they have significant limitations. These limitations include the fact that these lines only approximate megakaryocytes. These lines do not contain α-granules, do not demarcate or release platelets, respond appropriately to thrombopoietin (TPO), or express the high levels of such platelet-specific proteins such as the integrin αIIb and platelet factor 4 (PF4). Other proteins such as the platelet-restricted G protein G(z)α has not been detected in any of these cell lines. Further, these cell lines often express a mixture of multiple different lineages and can be easily shifted from one lineage to another.
6516 Background: BCR-ABL transcript levels have been reported to be a predictor of response outco... more 6516 Background: BCR-ABL transcript levels have been reported to be a predictor of response outcomes, including the detection of new mutations, in pts with imatinib resistance. In this posthoc anal...
6513 Background: Response dynamics in pts treated with nilotinib for imatinib failure may be diff... more 6513 Background: Response dynamics in pts treated with nilotinib for imatinib failure may be different than imatinib in front line. Many pts treated with nilotinib in the second line achieved cytogenetic responses early (median time to MCyR and CCyR of 2.8 mo and 3.3 mo). A previous landmark analysis demonstrated BCR-ABL% (IS) at 3 months (mo) on nilotinib predicted achievement of subsequent cytogenetic response. Here, we investigated whether early molecular response before 3 mo was associated with subsequent cytogenetic response. Methods: CML-CP pts (N = 321) with imatinib resistance or intolerance were grouped by 1 mo BCR-ABL% (IS) and landmark analyses were performed to evaluate probability of cytogenetic response with a minimum follow-up of 24 mo. Results: Early molecular response of BCR-ABL% (IS) ≤ 10 occurred in 19% of pts who received nilotinib. Pts with BCR-ABL% (IS) >1 – ≤10 (n = 37) had higher probability of MCyR by 12 mo (84%) compared with pts with BCR-ABL% (IS) >10 (55%) (n = 202). Pts with B...
BACKGROUND Intravenous TTI-621 (SIRPα-IgG1 Fc) was previously shown to have activity in relapsed ... more BACKGROUND Intravenous TTI-621 (SIRPα-IgG1 Fc) was previously shown to have activity in relapsed or refractory haematological malignancies. This phase 1 study evaluated the safety and activity of TTI-621 in patients with percutaneously accessible relapsed or refractory mycosis fungoides, Sézary syndrome, or solid tumours. Here we report the clinical and translational results among patients with mycosis fungoides or Sézary syndrome. METHODS This multicentre, open-label, phase 1 study was conducted at five academic health-care and research centres in the USA. Eligible patients were aged 18 years or older; had injectable, histologically or cytologically confirmed relapsed or refractory cutaneous T-cell lymphoma (CTCL) or solid tumours; Eastern Cooperative Oncology Group performance status of 2 or less; and adequate haematological, renal, hepatic, and cardiac function. TTI-621 was injected intralesionally in a sequential dose escalation (cohorts 1-5; single 1 mg, 3 mg, or 10 mg injection or three 10 mg injections weekly for 1 or 2 weeks) and in expansion cohorts (cohorts 6-9; 2 week induction at the maximum tolerated dose; weekly continuation was allowed). In cohort 6, patients were injected with TTI-621 in a single lesion and in cohort 7, they were injected in multiple lesions. In cohort 8, TTI-621 was combined with pembrolizumab 200 mg injections per product labels. In cohort 9, TTI-621 was combined with the standard labelled dose of subcutaneous pegylated interferon alpha-2a 90 μg. The primary endpoint was the incidence and severity of adverse events. The study is registered with ClinicalTrials.gov, NCT02890368, and was closed by the sponsor to focus on intravenous studies with TTI-621. FINDINGS Between Jan 30, 2017, and March 31, 2020, 66 patients with mycosis fungoides, Sézary syndrome, other CTCL, or solid tumours were screened, 35 of whom with mycosis fungoides or Sézary syndrome were enrolled and received intralesional TTI-621 (escalation, n=13; expansion, n=22). No dose-limiting toxicities occurred; the maximum tolerated dose was not established. In the dose expansion cohorts, the maximally assessed regimen (10 mg thrice weekly for 2 weeks) was used. 25 (71%) patients had treatment-related adverse events; the most common (occurring in ≥10% of patients) were chills (in ten [29%] patients), injection site pain (nine [26%]), and fatigue (eight [23%]). No treatment-related adverse events were grade 3 or more or serious. There were no treatment-related deaths. Rapid responses (median 45 days, IQR 17-66) occurred independently of disease stage or injection frequency. 26 (90%) of 29 evaluable patients had decreased Composite Assessment of Index Lesion Severity (CAILS) scores; ten (34%) had a decrease in CAILS score of 50% or more (CAILS response). CAILS score reductions occurred in adjacent non-injected lesions in eight (80%) of ten patients with paired assessments and in distal non-injected lesions in one additional patient. INTERPRETATION Intralesional TTI-621 was well tolerated and had activity in adjacent or distal non-injected lesions in patients with relapsed or refractory mycosis fungoides or Sézary syndrome, suggesting it has systemic and locoregional abscopal effects and potential as an immunotherapy for these conditions. FUNDING Trillium Therapeutics.
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