Faculty Bibliography

Background: Treatment strategies for patients (pts) with relapsed/refractory (RR) classical Hodgkin lymphoma (cHL) continue to evolve as brentuximab vedotin (BV) and immune checkpoint inhibitors are utilized in pre-transplant salvage regimens. These new approaches are based on promising results of non-randomized trials, but it is not clear how they perform outside of clinical studies. We aimed to investigate selection patterns, toxicities, and outcomes of salvage regimens prior stem cell transplant (SCT) used currently in the United States for pts with RR cHL in the non-trial setting.
Method(s): We conducted a multisite, retrospective study of pts with RR cHL who were treated with a first salvage regimen (salvage 1) with intent to proceed to SCT within the past 5 years. Only pts who were treated outside of a clinical trial with salvage 1 were included. Responses were based on treating physician assessment using Revised Response Criteria for Malignant Lymphoma (Cheson et al, JCO 2014). Kaplan Meier survival curves were generated using STATA 15.0 software.
Result(s): We identified 160 pts with diagnosis of RR cHL from 6 U.S. centers who received salvage 1 in the non-trial setting between January 2013 and January 2018. The pts' characteristics are described in Table 1. Both primary refractory pts (41%) and those with relapsed disease (59%) were included. The most common salvage 1 regimen for RR cHL was ifosfamide, carboplatin, etoposide (ICE) in 68% followed by BV monotherapy (14%) and BV+bendamustine (9%). Only 1 pt (1%) received immune checkpoint inhibitor. There were no statistically significant factors that would increase likelihood of receiving BV-containing salvage 1 including primary refractory status, age, and advanced stage. In the cohort of 59 pts who required more than one line of salvage therapy, the most common second salvage regimen (salvage 2) was BV monotherapy (42%), followed by various BV-containing combinations (22%), and ICE (19%). Only 14% of pts received 3 or more lines of salvage therapy prior to SCT. Out of 107 pts who received ICE as salvage 1, 33% were administered second salvage while out of 35 pts who received BV-containing regimen as salvage 1, 53% required salvage 2 (X²=4.7, p=0.03). Of 148 pts who ultimately underwent SCT, 52% were exposed to BV and 12% to an immune checkpoint inhibitor as part of any salvage regimen at some point prior to SCT. Response assessment to salvage 1 were available for 154 pts; 47% pts achieved complete response (CR), 30% partial response (PR), and 19% had progressive disease (PD). The responses to specific salvage 1 regimens are summarized in Table 2. For those pts undergoing salvage 2, 48% achieved CR, 19% PR and 30% had PD. Radiation was administered to 11% of pts at any point of salvage treatment prior SCT. In terms of toxicities, there were no deaths attributed to complications from any of the salvage therapies. When compared to ICE, pts undergoing BV or BV+bendamustine as salvage 1 had lower risk of neutropenic fever (0% vs 7%) and GI toxicities (10% vs 18%), but had higher risk of experiencing peripheral neuropathy (5% vs 15%). Out of 148 pts who ultimately underwent SCT, the majority had autologous (96%) and 6 (4%) pts had allogeneic SCT. The majority (73%) of patients were in CR immediately prior SCT. Four pts (3%) died due to SCT-related toxicities. BV maintenance was used in 35% of pts. Exposure to BV during salvage 1 prior SCT did not affect the likelihood of receiving BV maintenance. While there was no statistically significant difference in progression free survival (PFS) between chemotherapy only and BV-containing salvage 1, there was a trend toward improved PFS with BV-containing salvage 1 as shown in Figure 1. The 2-year PFS for chemotherapy only salvage 1 was 71% (95% CI: 60-79%) vs. 80% (95% CI: 60-91%) for BV-containing salvage treatments.
Conclusion(s): Growing number of salvage regimens are used in RR cHL. In the current practice outside of clinical trials, 23% of RR cHL pts received BV during salvage 1. In total, 37% received more than one salvage treatment and 52% received BV as part of salvage therapy prior SCT. It is unlikely that a prospective randomized trial will be conducted to compare various salvage treatment options. However, further analysis of sub-populations who may benefit from a particular regimen or optimal treatment sequences may lead to more effective and less toxic treatment strategies for pts with RR cHL. [Formula presented] Disclosures: Svoboda: Seattle Genetics: Consultancy, Research Funding; BMS: Consultancy, Research Funding; Merck: Research Funding; Incyte: Research Funding; Pharmacyclics: Consultancy, Research Funding; AstraZeneca: Consultancy; Celgene: Research Funding; Kyowa: Consultancy; Kite: Consultancy. Andreadis: Genentech: Equity Ownership, Other: Spouse is Employee; Novartis: Honoraria, Research Funding; Amgen: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Gilead: Consultancy; Jazz Pharmaceuticals: Consultancy; Bayer: Consultancy. Feldman: Portola Pharma: Research Funding; Eisai: Research Funding; Kyowa Hakko Kirin: Research Funding; Janssen: Honoraria, Speakers Bureau; Pharmacyclics: Honoraria, Other: Travel expenses, Speakers Bureau; AbbVie: Honoraria, Other: Travel expenses, Speakers Bureau; Roche: Research Funding; Viracta: Research Funding; Trillium: Research Funding; Pfizer: Research Funding; Seattle Genetics: Consultancy, Honoraria, Other: Travel expenses, Speakers Bureau; Kite Pharma: Honoraria, Other: Travel expenses, Speakers Bureau; Bayer: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Research Funding; Corvus: Research Funding; Roche: Research Funding; Cell Medica: Research Funding; Takeda: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding, Speakers Bureau. Khan: Back Bay Life Science Advisors: Honoraria; ASCO/Conquer Cancer Foundation sponsored by Gilead Sciences: Research Funding. Moskowitz: ADC Therapeutics: Consultancy; Cell Medica: Consultancy; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda Pharmaceuticals: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Cell Medica: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; Cell Medica: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Merck: Research Funding; Merck: Research Funding; ADC Therapeutics: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Cell Medica: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; ADC Therapeutics: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; Merck: Research Funding; Merck: Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; ADC Therapeutics: Consultancy; Incyte: Research Funding; Cell Medica: Consultancy; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Cell Medica: Consultancy; miRagen Therapeutics Inc: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Incyte: Research Funding; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; ADC Therapeutics: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Erytech Pharma: Consultancy; Merck: Research Funding; Incyte: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Cell Medica: Consultancy; Takeda Pharmaceuticals: Consultancy; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; Incyte: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Takeda Pharmaceuticals: Consultancy; Merck: Research Funding; Merck: Research Funding; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Erytech Pharma: Consultancy; Seattle Genetics: Consultancy, Honoraria, Research Funding; Merck: Research Funding; Merck: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Cell Medica: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Erytech Pharma: Consultancy; Takeda Pharmaceuticals: Consultancy; Bristol-Myers Squibb: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Cell Medica: Consultancy; Cell Medica: Consultancy; Incyte: Research Funding; Incyte: Research Funding; Cell Medica: Consultancy; ADC Therapeutics: Consultancy; Incyte: Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Merck: Research Funding; Bristol-Myers Squibb: Consultancy, Research Funding; miRagen Therapeutics Inc: Consultancy, Research Funding; Takeda Pharmaceuticals: Consultancy; Kyowa Hakko Kirin Pharma: Consultancy, Research Funding; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; ADC Therapeutics: Consultancy; Incyte: Research Funding; Takeda Pharmaceuticals: Consultancy; Incyte: Research Funding; Incyte: Research Funding; Seattle Genetics: Consultancy, Honoraria, Research Funding. Portell: Roche/Genentech: Research Funding; Xencor: Research Funding; TG Therapeutics: Research Funding; Acerta/AstraZeneca: Research Funding; Kite: Consultancy, Research Funding; BeiGene: Consultancy, Research Funding; Bayer: Consultancy; Amgen: Consultancy; Genentech: Consultancy, Research Funding; Janssen: Consultancy; Pharmacyclics: Consultancy; AbbVie: Research Funding; Infinity: Research Funding. Dwivedy Nasta: Merck: Consultancy, Other: data safety monitorin; 47 (Forty Seven): Research Funding; Roche: Research Funding; Rafael: Research Funding; Debiopharm: Research Funding; Aileron: Research Funding; ATARA: Research Funding; Pharmacyclics: Research Funding; Celgene: Honoraria; Millenium/takeda: Research Funding. Landsburg: Takeda: Research Funding; Celgene: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Curis, INC: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Seattle Genetics: Speakers Bureau; Seattle Genetics: Speakers Bureau; Takeda: Research Funding; Triphase: Research Funding; Triphase: Research Funding. Barta: Mundipharma: Honoraria; Seattle Genetics: Honoraria, Research Funding; Takeda: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Mundipharma: Honoraria; Bayer: Consultancy, Research Funding; Merck: Research Funding; Celgene: Research Funding; Janssen: Membership on an entity's Board of Directors or advisory committees. Chong: Tessa: Consultancy; Merck: Research Funding; Novartis: Consultancy. Schuster: Acerta: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Honoraria; Nordic Nanovector: Consultancy, Honoraria; Genentech: Consultancy, Honoraria, Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Merck: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Pharmacyclics: Consultancy, Honoraria, Research Funding; Loxo Oncology: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Celgene: Consultancy, Honoraria, Research Funding; Novartis: Honoraria, Patents & Royalties: Combination CAR-T and PD-1 Inhibitors, Research Funding. OffLabel Disclosure: Brentaximab vedotin containing salvage in Hodgkin lymphoma
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Background: Despite recent advances, follicular lymphoma (FL) remains incurable for most patients (pts). Relapsed/refractory (r/r) FL is associated with decremental treatment responses, accumulating toxicity, and poor survival among early failures of 1st line chemoimmunotherapy. Underscored by the recent approvals of idelalisib, copanlisib, and duvelisib, targeting B-cell receptor (BCR) signaling produces ORR of ~50% in r/r pts; however, new agents with a better therapeutic index over long-term administration are needed. SYK is a key regulator of BCR signaling (upstream of BTK and PI3K), and its inhibition results in clinical activity in FL. Compared with unaffected nodes, lymph nodes from FL pts have greater numbers of follicular helper T cells that express high levels of IL-4, which may support the tumor via the JAK1/3 pathway. Cerdulatinib, an oral, reversible inhibitor of SYK and JAK kinases (JAK1, JAK3, TYK2), previously reported a ~45% ORR in r/r FL as a single agent. Xenograft studies suggest cerdulatinib may combine with rituximab to enhance antitumor activity. We report updated results from a Ph2a study of single-agent cerdulatinib and initial results in combination with rituximab in r/r FL.
Method(s): This Ph2a study confirmed the safety and efficacy of cerdulatinib 30 mg BID in r/r B- and T-cell lymphoma pts. Dose reductions were permitted to 15 mg BID. Response was assessed by Lugano criteria.
Result(s): As of Jan 2019, enrollment was 40 pts in the single-agent cohort and 11 in the rituximab combination cohort. Median (range) age was 64 (42-81) and median prior therapies was 3 (1-8). Fifty (98%) pts had prior anti-CD20 therapy, and 8 (16%) had prior PI3K or BTK inhibitors. The most common AEs of any grade were diarrhea (47%), nausea (37%), lipase increase (29%), and amylase increase (22%). Grade 3+ AEs in >=5% pts were lipase increase (24%), diarrhea (12%), amylase increase (10%), nausea (8%), hypertension (8%), and neutropenia (6%). Grade 3+ infections occurred in 6 (12%) pts. One pt had grade 5 multi-organ failure potentially related to study drug. Amylase and lipase increases generally were not associated with abdominal pain or pancreatitis. The safety profile appeared similar in both cohorts. The ORR was 46% as a single agent (5 CRs, 13 PRs in 40 pts) and 67% in the combination cohort (4/6 PRs; 2 pts with SD had a >40% reduction in tumor volume at 1st re-scan). Responses typically occurred after 2 cycles and were durable in the single-agent cohort, with 10 pts on drug for >1 year. Enrollment in the combination cohort is ongoing. Updated safety and efficacy will be presented.
Conclusion(s): The recommended cerdulatinib Ph2 dose of 30 mg BID was tolerable and efficacious in heavily pretreated r/r FL. The cerdulatinib + rituximab combination appears to be well tolerated, with tumor reductions in all evaluable pts. The safety profile and unique MOA of cerdulatinib support further combination studies in FL

Background: Despite recent advances, follicular lymphoma (FL) remains incurable for most patients. Relapsed/refractory (r/r) FL is associated with decremental treatment responses, accumulating toxicity, and poor survival among early failures of front-line chemoimmunotherapy. Underscored by the recent approvals of idelalisib, copanlisib, and duvelisib, targeting kinases involved in B-cell antigen receptor (BCR) signaling produces responses in ~50% of r/r patients; however, new agents with a more favorable therapeutic index over long-term administration are needed. SYK is a key regulator of BCR signaling (upstream of BTK and PI3K), and its inhibition demonstrates clinical activity in B-cell malignancies. Study of the FL tumor microenvironment suggests an IL-4 signaling axis critical for survival. Compared with unaffected nodes, lymph nodes from patients with FL have greater numbers of follicular helper T cells that express high levels of IL-4, which may support the tumor via JAK1/3 pathway activation. Cerdulatinib is an oral, reversible ATP-competitive dual inhibitor of SYK and JAK family kinases (JAK1, JAK3, and TYK2) being investigated for the treatment of r/r FL, and previously reported a ~45% ORR in r/r FL when used as a single agent. Xenograft studies suggest cerdulatinib may combine with rituximab to enhance antitumor activity.
Aim(s): We report herein updated results from a phase 2a dose-expansion study of single-agent cerdulatinib and initial results for cerdulatinib in combination with rituximab in r/r FL.
Method(s): This phase 2a study confirmed the safety and efficacy of cerdulatinib 30 mg orally BID in patients with r/r B- and T-cell lymphoma. Dose reductions were permitted to a minimum of 15 mg BID. Response was assessed by Lugano Classification criteria.
Result(s): As of January 23, 2019, 40 patients have enrolled in the single- agent cohort and 11 have enrolled in the rituximab combination cohort. Median (range) age was 64 (42-81) and median number of prior therapies was 3 (1-8). Fifty (98%) patients had prior anti-CD20 therapy, and 8 (16%) patients had prior PI3K or BTK inhibitors. The most common AEs of any grade were diarrhea (47%), nausea (37%), lipase increase (29%), and amylase increase (22%). Grade 3+ AEs in >=5% of patients were lipase increase (24%), diarrhea (12%), amylase increase (10%), nausea (8%), hypertension (8%), and neutropenia (6%). Grade 3+ infections occurred in 6 (12%) patients. One patient had grade 5 multi-organ failure potentially related to study drug. Amylase and lipase elevations generally were not associated with abdominal pain or pancreatitis. The safety profile in the combination cohort appeared similar to that of single-agent cerdulatinib. Responses were seen in both cohorts: ORR of 46% (5/40 CRs; 13/40 PRs) in the single-agent cohort and ORR of 67% (4/6 PRs; both patients with SD demonstrated >40% reduction in baseline target tumors at first re-scan) in the combination cohort. Responses typically occurred after 2 cycles of treatment. Responses were durable in the single-agent cohort, with 10 patients on drug for >1 year. Enrollment in the combination cohort is ongoing. Updated safety and efficacy will be presented. Summary/Conclusion: The recommended cerdulatinib phase 2 dose of 30 mg BID demonstrated good tolerability and efficacy in heavily pretreated r/r FL. The combination of cerdulatinib with rituximab appears to be well tolerated and led to tumor reductions in all patients evaluated. The safety profile and unique mechanism of action of cerdulatinib support further combination studies in FL

Purpose Patients with double-hit lymphoma (DHL) rarely achieve long-term survival following disease relapse. Some patients with DHL undergo consolidative autologous stem-cell transplantation (autoSCT) to reduce the risk of relapse, although the benefit of this treatment strategy is unclear. Methods Patients with DHL who achieved first complete remission following completion of front-line therapy with either rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) or intensive front-line therapy, and deemed fit for autoSCT, were included. A landmark analysis was performed, with time zero defined as 3 months after completion of front-line therapy. Patients who experienced relapse before or who were not followed until that time were excluded. Results Relapse-free survival (RFS) and overall survival (OS) rates at 3 years were 80% and 87%, respectively, for all patients (n = 159). Three-year RFS and OS rates did not differ significantly for autoSCT (n = 62) versus non-autoSCT patients (n = 97), but 3-year RFS was inferior in patients who received R-CHOP compared with intensive therapy (56% v 88%; P = .002). Three-year RFS and OS did not differ significantly for patients in the R-CHOP or intensive therapy cohorts when analyzed by receipt of autoSCT. The median OS following relapse was 8.6 months. Conclusion In the largest reported series, to our knowledge, of patients with DHL to achieve first complete remission, consolidative autoSCT was not associated with improved 3-year RFS or OS. In addition, patients treated with R-CHOP experienced inferior 3-year RFS compared with those who received intensive front-line therapy. When considered in conjunction with reports of patients with newly diagnosed DHL, which demonstrate lower rates of disease response to R-CHOP compared with intensive front-line therapy, our findings further support the use of intensive front-line therapy for this patient population.

This phase 2 study evaluated brentuximab vedotin monotherapy in CD30-expressing DLBCL; after several patients with little to no CD30 achieved a complete remission (CR), the study evaluated treatment of DLBCL with undetectable CD30 (CD30u) by local visual immunohistochemistry (vIHC). Sixteen of 52 CD30u DLBCL patients (31%) had an objective response (6 CRs [12%]). Median progression-free survival (PFS) was 1.4 months (range, 0.4-15.6) and median overall survival (OS) was 7.5 months (range, 0.7-18.6+). Subsequent CD30 expression quantitated by computer-assisted digital image analysis (cIHC) showed that 11 of 16 CD30u DLBCL responders had >/=1% CD30. Correlative analyses of CD30u and CD30-expressing DLBCL combined demonstrated that >/=1% CD30 expression by cIHC resulted in a trend toward a higher response rate and significantly longer median PFS and OS. A minimum CD30 expression threshold appears to be required for antitumor activity in DLBCL; however, other factors also likely contribute to activity. (NCT01421667).

BACKGROUND: Long-term survival in patients with aggressive peripheral T-cell lymphoma (PTCL) is generally poor, and there currently is no clear consensus regarding the initial therapy used for these diseases. Herein, the authors analyzed treatment patterns and outcomes in a prospectively collected cohort of patients with a new diagnosis of nodal PTCL in the United States. METHODS: Comprehensive Oncology Measures for Peripheral T-cell Lymphoma Treatment (COMPLETE) is a prospective multicenter cohort study designed to identify the most common prevailing treatment patterns used for patients newly diagnosed with PTCL in the United States. Patients with nodal PTCL and completed records regarding baseline characteristics and initial therapy were included in this analysis. All statistical tests were 2-sided. RESULTS: Of a total of 499 patients enrolled, 256 (51.3%) had nodal PTCL and completed treatment records. As initial therapy, patients received doxorubicin-containing regimens (41.8%), regimens containing doxorubicin plus etoposide (20.9%), other etoposide regimens (15.8%), other single-agent or combination regimens (19.2%), and gemcitabine-containing regimens (2.1%). Survival was found to be statistically significantly longer for patients who received doxorubicin (log-rank P = .03). After controlling for disease histology and International Prognostic Index, results demonstrated a trend toward significance in mortality reduction in patients who received doxorubicin compared with those who did not (hazard ratio, 0.71; 95% confidence interval, 0.48-1.05 [P = .09]). CONCLUSIONS: To the authors' knowledge, there is no clear standard of care in the treatment of patients with PTCL in the United States. Although efforts to improve frontline treatments are necessary, anthracyclines remain an important component of initial therapy for curative intent. Cancer 2017;123:1174-1183. (c) 2016 American Cancer Society.

BACKGROUND: High response rates for doxorubicin HCl liposome injection (DLI) in cutaneous T-cell lymphoma (CTCL) have been reported with vague criteria until recently. Approximately 50% of CTCL patients respond to bexarotene (Bex). PATIENTS AND METHODS: A phase II trial was carried out to clarify the true overall response rate (ORR) for DLI and to assess the role of sequential Bex. Patients were treated with DLI 20 mg/m(2) i.v. every 2 weeks for 16 weeks (8 doses) followed by 16 weeks with Bex 300 mg/m(2) orally. Response assessments were carried out after 16 (DLI) and 32 weeks (Bex). Skin responses were measured by the modified Severity-Weighted Assessment Tool (mSWAT) and the Composite Assessment of Index Lesion Severity (CA). RESULTS: Thirty-seven patients were treated: stage IV (22, 8 with Sezary syndrome), IIB (10), earlier stage refractory to skin-directed therapies or radiation therapy (5). For 34 assessable patients: ORR 14/34 [41%: partial response (PR) 12, clinical complete response (CCR) 2]. Maximum responses were all seen after 16 weeks DLI. Median progression-free survival (PFS) was 5 months. There were 22 deaths: 21 of disease and 1 of heart failure. Twenty-seven grade 3 and 5 grade 4 toxic events were observed. CONCLUSION(S): With strict criteria, DLI ORR is among the highest reported for single agents in CTCL. Sequential Bex did not increase the response rate or duration.

Subtypes of diffuse large B-cell lymphoma (DLBCL) that have inferior outcomes after front-line therapy with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone) have been identified. While it is agreed that R-CHOP is probably not adequate in these patients, there is no standard treatment approach for patients with DLBCL with high-risk features. We present results of a retrospective cohort study of high-risk DLBCL (defined as having at least one unfavorable risk factor: non-germinal center [GC] subtype by immunohistochemistry [IHC], Ki-67 >/= 80%, high International Prognostic Index [IPI], c-MYC rearrangement) treated with R-HCVAD/R-MTX-AraC (rituximab, cyclophosphamide-fractionated, vincristine, doxorubicin and dexamethasone alternating with rituximab, methotrexate and cytarabine; R-HCVAD) as front-line therapy. With a median follow-up of 25.3 months, the 3-year PFS and OS estimates are 79% (95% confidence interval [CI], 65-88%) and 76% (95% CI, 61-86%), respectively, which are higher than those for historical comparisons with R-CHOP data for high-risk patients. These data are in accord with other recent reports of dose-intense front-line therapy of high-risk DLBCL. This analysis represents the largest reported cohort of patients with DLBCL treated with R-HCVAD. These data suggest that R-HCVAD can overcome traditional poor risk features such as high IPI, high Ki-67 and non-GC IHC pattern. Future work will focus on identifying molecular markers for failure in patients with DLBCL treated with dose-intensive regimens.

BACKGROUND: Although convincing data exist regarding the prognostic utility of positron emission tomographic (PET)-computed tomographic (CT) imaging in Hodgkin lymphoma and diffuse large B-cell lymphoma, its prognostic utility both during treatment and immediately after treatment have not been systematically evaluated in a large mantle cell lymphoma (MCL) patient cohort to support its use in clinical practice. METHODS: The authors conducted a retrospective cohort study to examine the prognostic utility of PET-CT imaging in a uniform MCL patient cohort undergoing dose-intensive chemotherapy (R-HyCVAD) in the frontline setting. The primary study endpoints were progression-free survival (PFS) and overall survival (OS). PET-CT images were centrally reviewed for the purposes of this study using standardized response criteria. RESULTS: Fifty-three patients with advanced stage MCL with PET-CT data were identified. With median follow-up of 32 months, 3-year PFS and OS estimates were 76% (95% confidence interval [CI], 64%-84%) and 84% (95% CI, 72%-90%), respectively. Interim PET-CT status was not associated with PFS (hazard ratio [HR], 0.9; 95% CI, 0.3-2.7; P = .8) or OS (HR, 0.6; 95% CI, 0.1-2.9; P = .5). Post-treatment PET-CT status was statistically significantly associated with PFS (HR, 5.2; 95% CI, 2.0-13.6; P = .001) and trended toward significant for OS (HR, 2.8; 95% CI, 0.8-9.6; P = .07). CONCLUSIONS: These data do not support the prognostic utility of PET-CT in pretreatment and interim treatment settings. A positive PET-CT after the completion of therapy identifies a patient subset with an inferior PFS and a trend toward inferior OS.