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ABVD (Adriamycin, bleomycin, vinblastine, dacarbazine) with or without radiation has been the standard treatment for limited-stage Hodgkin lymphoma (HL) but carries risks of bleomycin lung injury and radiation toxicity. Brentuximab vedotin (BV) is approved with AVD for stage III-IV HL, but carries increased risks of peripheral neuropathy (PN) and neutropenic fever, likely due to overlapping toxicity between BV and vinblastine. We therefore evaluated BV in combination with AD for 4 or 6 cycles based on interim positron emission tomography response. Thirty-four patients with nonbulky stage I-II HL were enrolled. Risk was early favorable in 53% and unfavorable in 47%. The overall and complete response rates (CRRs) were 100% and 97%, respectively, with a 5-year progression-free survival (PFS) of 91%. No differences in outcome were observed based on stage (I vs II) or risk status (early favorable vs unfavorable). The most common adverse events were nausea (85%), peripheral sensory neuropathy (59%), and fatigue (56%). There were no cases of grade-4 neutropenia or neutropenic fever, and no patient received granulocyte-colony stimulating factor. Most cases of PN were grade 1, and no patient experienced grade ≥3 PN. BV-AD produced a high CRR and durable PFS with most patients requiring 4 cycles of therapy. Compared with BV-AVD, the toxicity profile appeared improved, with predominantly grade 1 reversible PN and no case of grade 4 neutropenia or neutropenic fever. This regimen warrants further study in HL and may serve as a backbone for the addition of novel agents. This trial is registered on clinicaltrials.gov (NCT02505269).

•Brentuximab vedotin plus AD without radiation is an effective therapy for nonbulky limited-stage HL, with a favorable toxicity profile.•Risk of neutropenia, neutropenic fever, and grade ≥2 peripheral neuropathy appear significantly reduced compared with BV-AVD.

Pacritinib (SB1518) is a Janus kinase 2 (JAK2), JAK2(V617F), and Fms-like tyrosine kinase 3 inhibitor that does not inhibit JAK1. It demonstrated a favorable safety profile with promising efficacy in phase 1 studies in patients with primary and secondary myelofibrosis (MF). This multicenter phase 2 study further characterized the safety and efficacy of pacritinib in the treatment of patients with MF. Eligible patients had clinical splenomegaly poorly controlled with standard therapies or were newly diagnosed with intermediate- or high-risk Lille score. Patients with any degree of cytopenia were eligible. Thirty-five patients were enrolled. At entry, 40% had hemoglobin <10 g/dL and 43% had platelets <100 000× 109/L. Up to week 24, 8 of 26 evaluable patients (31%) achieved a ≥35% decrease in spleen volume determined by magnetic resonance imaging and 14 of 33 (42%) attained a ≥50% reduction in spleen size by physical examination. Median MF symptom improvement was ≥50% for all symptoms except fatigue. Grade 1 or 2 diarrhea (69%) and nausea (49%) were the most common treatment-emergent adverse events. The study drug was discontinued in 9 patients (26%) due to adverse events (4 severe). Pacritinib is an active agent in patients with MF, offering a potential treatment option for patients with preexisting anemia and thrombocytopenia. This trial was registered at www.clinicaltrials.gov as #NCT00745550.

Pacritinib (SB1518) is a Janus kinase 2 (JAK2), JAK2(V617F), and Fms-like tyrosine kinase 3 inhibitor that does not inhibit JAK1. It demonstrated a favorable safety profile with promising efficacy in phase 1 studies in patients with primary and secondary myelofibrosis (MF). This multicenter phase 2 study further characterized the safety and efficacy of pacritinib in the treatment of patients with MF. Eligible patients had clinical splenomegaly poorly controlled with standard therapies or were newly diagnosed with intermediate- or high-risk Lille score. Patients with any degree of cytopenia were eligible. Thirty-five patients were enrolled. At entry, 40% had hemoglobin <10 g/dL and 43% had platelets <100 000× 109/L. Up to week 24, 8 of 26 evaluable patients (31%) achieved a ≥35% decrease in spleen volume determined by magnetic resonance imaging and 14 of 33 (42%) attained a ≥50% reduction in spleen size by physical examination. Median MF symptom improvement was ≥50% for all symptoms except fatigue. Grade 1 or 2 diarrhea (69%) and nausea (49%) were the most common treatment-emergent adverse events. The study drug was discontinued in 9 patients (26%) due to adverse events (4 severe). Pacritinib is an active agent in patients with MF, offering a potential treatment option for patients with preexisting anemia and thrombocytopenia. This trial was registered at www.clinicaltrials.govas #NCT00745550.

Introduction:

Shah: Incyte: Research Funding; Jazz Pharmaceuticals: Research Funding; Servier Genetics: Other; BeiGene: Consultancy, Honoraria; Acrotech/Spectrum: Honoraria; Pharmacyclics/Janssen: Honoraria, Other: Expenses; Kite, a Gilead Company: Consultancy, Honoraria, Other: Expenses, Research Funding; Precision Biosciences: Consultancy; Amgen: Consultancy; Novartis: Consultancy, Other: Expenses; Pfizer: Consultancy, Other: Expenses; Bristol-Myers Squibb/Celgene: Consultancy, Other: Expenses; Adaptive Biotechnologies: Consultancy. Chavez: Astra Zeneca: Research Funding; Novartis: Consultancy; Merck: Research Funding; Morphosys: Speakers Bureau; Adaptive Biotech: Research Funding; ADC Therapeutics: Consultancy, Research Funding; Beigene: Speakers Bureau; Kite/Gilead: Consultancy; karyopharm: Consultancy; Epizyme: Speakers Bureau; Abbvie: Consultancy. Sokol: Dren Bio: Membership on an entity's Board of Directors or advisory committees; Kyowa-Kirin: Membership on an entity's Board of Directors or advisory committees. Lancet: Celgene/BMS: Consultancy; Millenium Pharma/Takeda: Consultancy; Daiichi Sankyo: Consultancy; AbbVie: Consultancy; BerGenBio: Consultancy; ElevateBio Management: Consultancy; Agios: Consultancy; Astellas: Consultancy; Jazz: Consultancy.Vyxeos is being evaluated in the described trial for the treatment of relapsed or refractory acute lymphoblastic leukemia in adults.

Chavez: Karyopharm: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Bayer: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees; Kite: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees. Nodzon:Pfizer: Consultancy; Pharmacyclics: Consultancy; Genentech: Consultancy, Other: Speaker Fees; Abbvie: Other: Speaker Fees. Pinilla Ibarz:Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Takeda: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Janssen: Consultancy, Speakers Bureau; Teva: Consultancy; TG Therapeutics: Consultancy; Bayer: Speakers Bureau; Sanofi: Speakers Bureau.The combination of PD1:PDL1 Blockade (PDB) and ibrutinib will reverse T cell dysfunction commonly seen in CLL patients, potentiating more robust anti-infective and anti-tumor immune responses

Chavez: Genentech: Speakers Bureau; Kite Pharmaceuticals, Inc.: Membership on an entity's Board of Directors or advisory committees; Janssen Pharmaceuticals, Inc.: Speakers Bureau; Novartis: Membership on an entity's Board of Directors or advisory committees. Sandoval-Sus:Seattle Genetics: Membership on an entity's Board of Directors or advisory committees. Shah:Celgene/Juno: Honoraria; Kite/Gilead: Honoraria; Incyte: Research Funding; Jazz Pharmaceuticals: Research Funding; Pharmacyclics: Honoraria; Adaptive Biotechnologies: Honoraria; Spectrum/Astrotech: Honoraria; Novartis: Honoraria; AstraZeneca: Honoraria. Bello:Celgene: Speakers Bureau. Sokol:EUSA: Consultancy. Nodzon:Pfizer: Consultancy; Pharmacyclics: Consultancy; Genentech: Consultancy, Other: Speaker Fees; Abbvie: Other: Speaker Fees. Pinilla Ibarz:Bayer: Speakers Bureau; TG Therapeutics: Consultancy; Teva: Consultancy; Janssen: Consultancy, Speakers Bureau; Novartis: Consultancy; Bristol-Myers Squibb: Consultancy; Takeda: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Sanofi: Speakers Bureau.

Background:Chronic lymphocytic leukemia (CLL) is the most common chronic leukemia. Patients in active surveillance with untreated high-risk CLL (defined as presence of del17p or TP53, del11q or ATM mutation or unmutated IGVH) have an unmet need as they tend to progress rapidly and develop resistance to standard therapies. There is evidence that deferring treatment in high-risk patients may be detrimental due to a more aggressive course of disease and that patients with clonal evolution into high-risk features may fare even worse prognosis (Shanafelt et al, JCO 2006). The CLL12 trial (ibrutinib for asymptomatic high risk CLL patients, Langerbeins et al ICML2019) showed event (EFS) and progression (PFS) free survival benefit when compared to placebo. In addition, T-cell dysfunction and immunosuppressive environment have been shown in CLL. The rationale of the trial is that the combination of PD1:PDL1 Blockade (PDB) and ibrutinib will reverse T cell dysfunction commonly seen in CLL patients, potentiating more robust anti-infective and anti-tumor immune responses.

Background: The treatment of Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) has continued to evolve in recent years, offering the patients different therapeutic options. Venetoclax (ven) is a selective, small molecule inhibitor of B-cell receptor-2 (BCL-2) approved by the FDA for patients with newly diagnosed and relapsed/refractory CLL. Stratification based on tumor lysis syndrome (TLS) risk is recommended and may guide debulking strategies.

Background: New targeted therapies continue to show improved efficacy in various stages of chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), sparing patients from chemoimmunotherapy. However, cure remains elusive. Here, we present a front-line alternative based on a combination of high-dose methylprednisolone (HDMP) and ofatumumab, followed by consolidative therapy with lenalidomide plus ofatumumab.

Komrokji: Novartis: Honoraria, Speakers Bureau; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau; Celgene: Honoraria, Research Funding; Novartis: Honoraria, Speakers Bureau. Locke:Novartis Pharmaceuticals: Other: Scientific Advisor; Cellular BioMedicine Group Inc.: Consultancy; Kite Pharma: Other: Scientific Advisor. Kharfan-Dabaja:Seattle Genetics: Speakers Bureau; Incyte Corp: Speakers Bureau; Alexion Pharmaceuticals: Speakers Bureau. Sokol:Spectrum Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy; Mallinckrodt Pharmaceuticals: Consultancy.

Pinilla-Ibarz: Teva: Consultancy, Speakers Bureau; Pfizer: Consultancy, Other: Consulting & Advisory Role, Research Funding, Speakers Bureau; Novartis: Consultancy, Other: Consulting & Advisory Role, Research Funding; ARIAD Pharmaceuticals, Inc.: Consultancy, Other: Consulting & Advisory Role, Research Funding; BMS: Consultancy, Honoraria, Other: Consulting & Advisory Role, Speakers Bureau. Off Label Use: Lenalidomide for CLL. Komrokji:Pharmacylics: Speakers Bureau; Novartis: Research Funding, Speakers Bureau; Incyte: Consultancy; Celgene: Consultancy, Research Funding. Locke:Kite Pharma: Other: Scientific Advisory Boards.

Background

Background: With the introduction of new targeted drugs for the treatment of CLL, a new therapeutic paradigm is emerging where chemo-immunotherapy is being replaced by newer non-chemotherapy containing regimens with the goal to maintain long term responses while an oral drug is being administered. Based on demonstrated activity of ofatumumab (Ofa) and lenalidomide (len) as monotherapy, here we present the results of a sequential combination regimen consisting of high-dose methylprednisolone (HDMP) combined with Ofa, followed by consolidative therapy with Len in combination with Ofa.

Komrokji: Celgene: Consultancy, Research Funding; Incyte: Consultancy; Novartis: Research Funding, Speakers Bureau; Pharmacylics: Speakers Bureau. Sokol:Seatle Genetics: Research Funding; Celgene: Consultancy; Spectrum: Consultancy.