Browsing by Author "Pagel, John M."

Now showing 1 - 3 of 3
  • Thumbnail Image
    Item
    The Society for Immunotherapy of Cancer consensus statement on immunotherapy for the treatment of hematologic malignancies: multiple myeloma, lymphoma, and acute leukemia
    (BioMed Central, 2016-12-20) Boyiadzis, Michael; Bishop, Michael R.; Abonour, Rafat; Anderson, Kenneth C.; Ansell, Stephen M.; Avigan, David; Barbarotta, Lisa; Barrett, Austin John; Van Besien, Koen; Bergsagel, Leif; Borrello, Ivan; Brody, Joshua; Brufsky, Jill; Cairo, Mitchell; Chari, Ajai; Cohen, Adam; Cortes, Jorge; Forman, Stephen J.; Friedberg, Jonathan W.; Fuchs, Ephraim J.; Gore, Steven D.; Jagannath, Sundar; Kahl, Brad S; Kline, Justin; Kochenderfer, James N.; Kwak, Larry W.; Levy, Ronald; de Lima, Marcos; Litzow, Mark R.; Mahindra, Anuj; Miller, Jeffrey; Munshi, Nikhil C.; Orlowski, Robert Z.; Pagel, John M.; Porter, David L.; Russell, Stephen J.; Schwartz, Karl; Shipp, Margaret A.; Siegel, David; Stone, Richard M.; Tallman, Martin S.; Timmerman, John M.; Van Rhee, Frits; Waller, Edmund K.; Welsh, Ann; Werner, Michael; Wiernik, Peter H.; Dhodapkar, Madhav V.; Department of Medicine, IU School of Medicine
    Increasing knowledge concerning the biology of hematologic malignancies as well as the role of the immune system in the control of these diseases has led to the development and approval of immunotherapies that are resulting in impressive clinical responses. Therefore, the Society for Immunotherapy of Cancer (SITC) convened a hematologic malignancy Cancer Immunotherapy Guidelines panel consisting of physicians, nurses, patient advocates, and patients to develop consensus recommendations for the clinical application of immunotherapy for patients with multiple myeloma, lymphoma, and acute leukemia. These recommendations were developed following the previously established process based on the Institute of Medicine’s clinical practice guidelines. In doing so, a systematic literature search was performed for high-impact studies from 2004 to 2014 and was supplemented with further literature as identified by the panel. The consensus panel met in December of 2014 with the goal to generate consensus recommendations for the clinical use of immunotherapy in patients with hematologic malignancies. During this meeting, consensus panel voting along with discussion were used to rate and review the strength of the supporting evidence from the literature search. These consensus recommendations focus on issues related to patient selection, toxicity management, clinical endpoints, and the sequencing or combination of therapies. Overall, immunotherapy is rapidly emerging as an effective therapeutic strategy for the management of hematologic malignances. Evidence-based consensus recommendations for its clinical application are provided and will be updated as the field evolves.
  • Thumbnail Image
    Item
    The role of adjuvant chemotherapy in the management of acute promyelocytic leukemia differentiation syndrome
    (Frontiers Media, 2022-08-03) LaBella, Dominic; Regan, Samuel; Konig, Heiko; Egan, Daniel N.; Bailey, Neil A.; Mawad, Raya; Gilbert, Morgan; Pagel, John M.; Pu, Jeffrey J.; Medicine, School of Medicine
    Acute Promyelocytic Leukemia (APL) is characterized by the t(15;17) chromosomal translocation resulting in a PML-RARA fusion protein. The all-trans-retinoic acid (ATRA) and Arsenic Trioxide (ATO) only regimens have demonstrated success in treating low- and intermediate-risk patients. However, induction with ATRA/ATO only regimens have been showing increased incidence of differentiation syndrome (DS), a potentially lethal complication, traditionally treated with dexamethasone. We conducted a three-institution retrospective study, aiming to evaluate the role of short-term adjuvant chemotherapy in managing moderate DS for patients with low- or intermediate-risk APL initially treated with ATRA/ATO only protocols. We evaluated the difference in incidence and duration of moderate DS in APL patients who were treated with ATRA/ATO with or without adjuvant chemotherapy. 57 low- or intermediate-risk APL patients were retrospectively identified and included for this study; 36 patients received ATRA/ATO only induction treatment, and 21 patients received ATRA/ATO/adjuvant chemotherapy combination induction therapy. Similar proportions of patients experienced DS in both groups (66.7% vs. 81.0%, P = 0.246). The median duration of DS resolution in patients receiving ATRA/ATO only was 17 days (n = 23), and in patients receiving combination therapy was 8 days (n = 16) (P = 0.0001). The lengths of hospital stay in patients receiving ATRO/ATO only was 38 days (n = 7), and in patients receiving combination therapy was 14 days (n = 17) (P = 0.0007). In conclusion, adding adjuvant chemotherapy to ATRA/ATO only protocol may reduce the duration of DS and the length of hospital stay during APL induction treatment.
  • Thumbnail Image
    Item
    Zandelisib with continuous or intermittent dosing as monotherapy or in combination with rituximab in patients with relapsed or refractory B-cell malignancy: a multicentre, first-in-patient, dose-escalation and dose-expansion, phase 1b trial
    (Elsevier, 2022) Pagel, John M.; Soumerai, Jacob D.; Reddy, Nishitha; Jagadeesh, Deepa; Stathis, Anastasios; Asch, Adam; Salman, Huda; Kenkre, Vaishalee P.; Iasonos, Alexia; Llorin-Sangalang, Judith; Li, Joanne; Zelenetz, Andrew D.; Medicine, School of Medicine
    Background: Phosphatidylinositol 3-kinase p110δ (PI3Kδ) inhibitors are efficacious in B-cell malignancies. Immune-related adverse events might be mitigated with intermittent dosing. We aimed to evaluate the safety and antitumour activity of zandelisib, a potent novel PI3Kδ inhibitor, with continuous or intermittent dosing as monotherapy or in combination with rituximab, in patients with relapsed or refractory B-cell malignancy. Methods: We conducted a first-in-patient, dose-escalation and dose-expansion, phase 1b trial at ten treatment centres across Switzerland and the USA. Eligible patients were aged 18 years or older with relapsed or refractory B-cell malignancy (limited to follicular lymphoma or chronic lymphocytic leukaemia during dose escalation) and an Eastern Cooperative Oncology Group performance status of 0-2, and had received at least one previous line of therapy and no previous PI3Kδ inhibitor treatment. In the dose-escalation study, participants received oral zandelisib once daily (60 mg, 120 mg, or 180 mg; we did not evaluate four additional planned dose levels). The 60 mg dose was further evaluated as monotherapy or with intravenous rituximab 375 mg/m2 on days 1, 8, 15, and 22 of cycle 1 and day 1 of cycles 3-6, using a continuous daily schedule or intermittent dosing therapy (days 1-28 of cycles 1-2 and days 1-7 of subsequent cycles) in 28-day cycles. Treatment was continued until evidence of disease progression, intolerance, or withdrawal of consent by the patient. Primary endpoints were safety (dose-limiting toxicities and maximum tolerated dose), minimum biologically effective dose, and a composite endpoint to assess the activity of each dose level, and were analysed by intention to treat. The zandelisib monotherapy and zandelisib-rituximab combination cohorts have completed accrual, but accrual to a cohort evaluating zandelisib with zanubrutinib is ongoing. This study is registered with ClinicalTrials.gov, NCT02914938. Findings: Between Nov 17, 2016, and June 2, 2020, 100 patients were assessed for eligibility and 97 were enrolled and received zandelisib monotherapy (n=56) or zandelisib plus rituximab (n=41), with zandelisib administered on either a continuous schedule (n=38) or with intermittent dosing (n=59). No dose-limiting toxicities were observed, the objective of determining the maximum tolerated dose was abandoned, and antitumour activity was similar across the evaluated doses activity (objective responses in 11 [92%; 95% CI 61·5-99·8] of 12 patients at both 60 mg and 120 mg doses, and in five [83%; 95% CI 35·9-99·6] of six patients at 180 mg). With a median duration of exposure of 15·2 months (IQR 3·7-21·7), the most common grade 3-4 adverse events were neutrophil count decrease (ten [17%] of 59 patients in the intermittent dosing group and four [11%] of 38 in the continuous dosing group), diarrhoea (three [5%] and eight [21%]), pneumonia (one [2%] and six [16%]), alanine aminotransferase increase (three [5%] and two [5%]), and colitis (two [3%] and one [3%]). 26 (44%) of 59 patients in the intermittent dosing group and 29 (76%) of 38 patients in the continuous dosing group had grade 3-4 adverse events. Treatment-related serious adverse events occurred in eight (21%) patients in the continuous dosing group and five (8%) patients in the intermittent dosing group. There were no treatment-related deaths. Interpretation: Zandelisib 60 mg once daily on an intermittent dosing schedule was safe, with low frequency of grade 3 or worse adverse events, warranting the ongoing global phase 2 and phase 3 trials.