Specialty Pharmacy and Physician Partnership Optimizes Clinical Pathway Adherence in Myelofibrosis (MF): Initial Analysis of a Quality Improvement Initiative

Background: MF patients (pts) can have significant disease-associated symptoms. Guidelines recommend evaluation of pts' symptom burdens and prognostic risk scores at clinic visits. The myeloproliferative neoplasm symptom assessment form total symptom score (MPN-SAF TSS) is a standardized system that evaluates 10 specific MPN-related symptoms on a scale of 1-10. Furthermore, the dynamic prognostic scoring system plus (DIPSS plus) has been validated as a risk stratification tool for MF pts at any point during the disease course. At our institution, leukemia physicians have created an MF pathway to guide practitioners throughout a large healthcare system with many locations. The pathway recommends MPN-SAF TSS and DIPSS plus risk score with clinic visits occurring every 3-6 months. Unfortunately, the traditional approach to obtaining the MPN-SAF TSS and DIPSS plus score is burdensome for many providers and pts. Moreover, a recent analysis (Verstovsek Ann Hematol 2020) demonstrates that risk prognostication is very often performed incorrectly. We designed a study to streamline workflow by incorporating our specialty pharmacy to assist in the completion of the MPN-SAF TSS and DIPSS plus score via telephone prior to clinic visits. We hypothesized that partnership between our physicians and the specialty pharmacy may benefit pts by increasing adherence to the MF pathway. Methods: This study is conducted in two parts, a retrospective and a prospective phase. A review 12 months prior to start of study was completed to gain historical insight on provider adherence to the MF pathway, with attention to MPN-SAF TSS and DIPSS plus. Then, a prospective study was designed to include new or established MF pts. Pts would be followed for 12 months after start of study. The pilot study was open only at our largest site, home to a subspecialty leukemia clinic where disease-specific physicians practice. For pts who enroll in the prospective study, specialty pharmacists complete both the MPN-SAF TSS and the DIPSS plus score ~3 months via phone prior to clinic visits. Calls for each pt are completed within 10 days of the pt's next visit. If the pharmacist is unable to reach the pt, the physician is notified via EMR message. Completed assessments are documented in the EMR. All enrolled pts are evaluated for MF pathway adherence during the study period. Results: We reviewed system-wide charts for 12 months prior to March 1, 2020 to assess if DIPSS and/or MPN SAF forms were documented for MF patients. 79 MF pts, treated by 32 physicians, were identified. Patients in remission after allogeneic stem cell transplantation were excluded. 36 pts (46%) had the MPN-SAF TSS completed and 53 pts (67%) had DIPSS plus performed at least once in the preceding 12 months. 45 pts, treated by 8 physicians, were followed primarily at the pilot site. 27 pts (60%) had MPN-SAF TSS documented and 38 (84%) had DIPSS Plus performed at least once in the preceding 12 months. The prospective study was initiated on March 1, 2020. As of July 15, 2020, 32 patients have been screened for enrollment by treating physicians. This includes 3 newly diagnosed patients not included in the retrospective analysis. 22 pts have had their initial assessments completed. 2 pts could not be reached, 1 of which died prior to the next clinic visit, 2 pts declined the study, and 6 pts had not yet had clinic visits. Of the 22 pts consented and contacted for the study, 100% had the MPN-SAF TSS and DIPSS Plus score documented with their first visit during the study period. To date 11 pts (of the initial 22) have undergone reevaluation; 100% had the MPN-SAF TSS and DIPSS Plus score documented with their 3-month follow-up visit. Conclusion: Many practicing clinicians perform MPN-SAF TSS and DIPSS plus scores for MF pts. However, there are lapses in the uptake of both. At our institution, the DIPSS plus score is performed more commonly than the MPN-SAF TSS. This early analysis suggests that a telemedicine approach and partnership between specialty pharmacy and physicians can optimize clinical workflow. With the initial success of this pilot, our program is expanding study enrollment to include regional clinics. Due to the COVID19 pandemic, there is now heightened interest in telemedicine practices. Preliminary data from this study suggest that a multidisciplinary approach incorporating telemedicine for MF pts provides an effective approach to measuring patient symptom burdens and assigning prognostic categories. Figure Disclosures Chojecki: Novartis: Other: Investigator Meeting Attendance; Incyte: Research Funding. Shah:Incyte: Speakers Bureau; Pharmacyclics: Speakers Bureau. Knight:Foundation for Financial Planning: Research Funding. Ai:Celgene: Speakers Bureau; Incyte: Speakers Bureau. Avalos:Best Practice-Br Med J: Patents &amp; Royalties: receives royalties from a coauthored article on evaluation of neutropenia; Juno: Membership on an entity's Board of Directors or advisory committees. Copelan:Amgen: Membership on an entity's Board of Directors or advisory committees. Grunwald:Janssen: Research Funding; Genentech/Roche: Research Funding; Abbvie: Consultancy; Daiichi Sankyo: Consultancy; Abbvie: Consultancy; Abbvie: Consultancy; Trovagene: Consultancy; Incyte: Consultancy, Research Funding; Celgene: Consultancy; Incyte: Consultancy, Research Funding; Agios: Consultancy; Janssen: Research Funding; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Trovagene: Consultancy; Premier: Consultancy; Merck: Consultancy; Genentech/Roche: Research Funding; Forma Therapeutics: Research Funding; Agios: Consultancy; Celgene: Consultancy; Celgene: Consultancy; Cardinal Health: Consultancy; Pfizer: Consultancy; Trovagene: Consultancy; Premier: Consultancy; Astellas: Consultancy; Premier: Consultancy; Merck: Research Funding; Astellas: Consultancy; Merck: Consultancy; Genentech/Roche: Research Funding; Daiichi Sankyo: Consultancy; Agios: Consultancy; Amgen: Consultancy; Amgen: Consultancy; Cardinal Health: Consultancy; Merck: Consultancy; Cardinal Health: Consultancy; Pfizer: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Incyte: Consultancy, Research Funding; Forma Therapeutics: Research Funding; Forma Therapeutics: Research Funding. </jats:sec

Characteristics Affecting Durability and Tolerability of Imatinib in Patients Switched from Brand to Generic and Newly Diagnosed Patients Initially Prescribed Generic Imatinib for Chronic Myeloid Leukemia

Introduction Gleevec, Imatinib mesylate, is the first in class BCR-ABL tyrosine kinase inhibitor initially approved to treat CML. In February 2016, generic imatinib products became available. As generic products are not required to offer comparative efficacy and safety data, differences may arise. Small reports have found no significant differences in response durability and tolerability in patients transitioned from Gleevec to generic imatinib. Further, lower cost of generic products often influence treatment decisions and patient compliance. We sought to evaluate response durability, tolerability, financial costs, and adherence in patients with chronic phase CML (cpCML) who switched from Gleevec to generic imatinib and newly diagnosed cpCML patients initiated on generic imatinib. Methods We conducted a single-center, retrospective chart review of adult patients who received imatinib therapy for cpCML between June 1, 2015 to November 14, 2019. Patients who received ≥6 months of brand through the Specialty Pharmacy Service (SPS) at Atrium Health prior to switching to generic were included in Group 1 (Switch). Patients who initiated therapy with generic imatinib dispensed from SPS were included in Group 2 (New Start). Durability of response was described determined via peripheral blood BCR-ABL transcripts by PCR and reported major molecular response (MMR) after 12 months generic imatinib therapy. Additional factors characterizing the durability and tolerability of therapy included adverse effects due to drug, dose modifications, adherence rate, prescription cost per month, and frequency of switch between generic products. Results Of 298 patients assessed, 12 patients were evaluable. There were 7 Switch patients and 5 New Start patients. Figure 1. All 12 patients met WHO diagnostic cpCML criteria. No patients in either group had accelerated or blast phase CML, no patients received maintenance imatinib following allogeneic HCT. In the Switch Group, 4 patients (57%) achieved MMR after 12 months of generic therapy. Of the 3 patients that did not achieve MMR, 1 patient relocated prior to 12-month assessment, 1 patient was noted to be non-compliant, and 1 patient had several treatment delays and dose reductions due to toxicities. 1 New Start patient achieved MMR at 12 months. Of those not achieving MMR, 1 was started on a reduced dose (100 mg /day) due to renal dysfunction, 1 had a PDC of 49.10% due to treatment delays while receiving treatment for a different malignancy, and 2 patients had logarithmic decreases in BCR-ABL but had not crossed the MMR threshold after 12 months of therapy. 5 Switch patients (71.4%) reported at least 1 adverse effect related to therapy, 3 of these (42.9%) required dose reduction. The adverse effects requiring dose reductions in the New Start patients included thrombocytopenia (n=2) and myalgia (n=1). All New Start patients reported at least 1 adverse effect with none of these patients requiring a dose reduction. Cost stayed the same or was reduced for 85.7% of the Switch patients, 1 patient experienced a cost increase and did not have co-pay assistance, and 2 patients received copay assistance. Cost of generic therapy was &amp;lt;10/month in 85.7% of the Switch and 80% of the New Start patients. No patients experienced disease progression and PDC was &gt;90% after 12 months on generic therapy for 71.4% Switch patients and 80% New Start patients. Table 1. and Table 2. Conclusion Patients with cpCML switched from brand to generic imatinib and patients newly started on generic imatinib appear to have durable responses and tolerance to generic imatinib. Dose reductions and non-adherence may have contributed to inadequate disease control in patients not achieving MMR in both groups. Patients switched from brand to generic imatinib may develop new side effects necessitating dose reduction. Thrombocytopenia may be more common in patients switched from brand to generic imatinib. Adherence to brand and generic imatinib is high and medication is affordable with most patients paying &lt;10/month. Our study is limited by a small sample size and retrospective nature. Prospective large studies are needed to compare tolerability and durability differences between brand and generic imatinib and available imatinib generic products. Disclosures Knight: Foundation for Financial Planning: Research Funding. Ai:Celgene: Speakers Bureau; Incyte: Speakers Bureau. Grunwald:Premier: Consultancy; Astellas: Consultancy; Janssen: Research Funding; Merck: Research Funding; Janssen: Research Funding; Forma Therapeutics: Research Funding; Forma Therapeutics: Research Funding; Astellas: Consultancy; Premier: Consultancy; Trovagene: Consultancy; Trovagene: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Daiichi Sankyo: Consultancy; Trovagene: Consultancy; Abbvie: Consultancy; Abbvie: Consultancy; Agios: Consultancy; Daiichi Sankyo: Consultancy; Agios: Consultancy; Abbvie: Consultancy; Merck: Consultancy; Merck: Consultancy; Agios: Consultancy; Amgen: Consultancy; Amgen: Consultancy; Cardinal Health: Consultancy; Merck: Consultancy; Cardinal Health: Consultancy; Pfizer: Consultancy; Amgen: Consultancy; Pfizer: Consultancy; Cardinal Health: Consultancy; Celgene: Consultancy; Celgene: Consultancy; Pfizer: Consultancy; Incyte: Consultancy, Research Funding; Incyte: Consultancy, Research Funding; Celgene: Consultancy; Incyte: Consultancy, Research Funding; Genentech/Roche: Research Funding; Premier: Consultancy; Genentech/Roche: Research Funding; Genentech/Roche: Research Funding; Forma Therapeutics: Research Funding. Avalos:Juno: Membership on an entity's Board of Directors or advisory committees; Best Practice-Br Med J: Patents &amp; Royalties: receives royalties from a coauthored article on evaluation of neutropenia. Copelan:Amgen: Membership on an entity's Board of Directors or advisory committees. Chojecki:Novartis: Other: Investigator Meeting Attendance; Incyte: Research Funding. </jats:sec

Clinical Characteristics and Outcomes of AML Patients Treated with Frontline CPX 351 or HMA/Venetoclax: A Single Institution's Experience

Abstract Introduction: Treatment options for newly diagnosed patients (pts) with acute myeloid leukemia (AML) have historically been limited. The combination of a hypomethylating agent and venetoclax (HMA/Ven) has emerged as standard of care treatment for elderly and/or unfit pts with newly diagnosed AML. Liposomal cytarabine/daunorubicin (CPX-351) has also become standard of care therapy for pts with AML with myelodysplasia related changes or therapy-related AML. Despite being an intensive regimen, CPX-351 may have a more favorable toxicity profile compared to other intensive regimens. As a result, CPX-351 may be offered to older fit pts who may not have been candidates for traditional induction regimens. As the landscape for frontline treatment options evolves, there are now overlapping pt populations who may be eligible for either frontline treatment option. A retrospective study that included clinical trial pts demonstrated similar response rates in pts treated with HMA/Ven and CPX-351 (Asghari Blood 2019). Similarly, a study of secondary AML pts receiving HMA/Ven and CPX-351 showed no difference in remission rate or survival (Salhotra Am J Hematol 2021). There remains a shortage of data describing clinical characteristics of pts selected for and treated with standard-of-care HMA/Ven and CPX-351. We present a study on our center's experience. Methods: The purpose of this study was to evaluate the clinical characteristics and outcomes of adult pts with newly diagnosed AML who were treated with either CPX-351 or HMA/Ven as initial therapy. Consecutive pts treated with either of these two induction therapies between August 2017 and June 2021 were evaluated retrospectively. Pts were eligible for response evaluation if they received at least 3 doses of CPX-351 or 28 days (1 cycle) of venetoclax ("response cohort"). All pts treated with CPX-351 or HMA/Ven were included in survival analysis ("survival cohort"). Response assessment is based on ELN-2017 criteria. Pt characteristics were described and compared using Fisher's Exact tests. Kaplan-Meier methods were used to summarize overall survival, and log-rank tests were used for the comparison of frontline therapies. Cox proportional-hazards regression estimated hazard ratio (HR), 95% confidence interval (CI), and interactions between frontline therapy and age at induction start. Results : A total of 79 pts were identified receiving frontline HMA/Ven or CPX-351; 61 pts (77%) were evaluable for response. Of the response cohort, 21 (34%) were treated with CPX-351 and 40 (66%) with HMA/Ven; pt characteristics are described in Table 1. CPX-351 pts were younger at start of induction (P&amp;lt;0.001); many pts in both treatment groups had unfavorable ELN risk scores at diagnosis (CPX 43%, HMA/Ven 41%; P&amp;gt;0.99). 33% and 23% of the HMA/Ven cohort achieved CR and CRi respectively; in the CPX-351 cohort 57% and 5% achieved CR and CRi respectively. A greater fraction of CPX-351 pts proceeded to allogeneic stem cell transplant than HMA/Ven pts (67% vs 23%; P&amp;lt;0.001). No differences were detected in achievement of MRD negativity by flow cytometry (P=0.51) or molecular profile (P=0.52). Median follow-up for all pts was 18.9 months; 42 deaths occurred. Differences in survival between the frontline therapies were not detected in the survival cohort (HR, 1.31; 95% CI, 0.67 to 2.57; P=0.43) nor the response cohort (HR, 0.97; 95% CI, 0.45 to 2.09; P=0.93); these results were unaffected by adjustments for age at induction, ELN risk score, and transplant status. 8 pts who initially received CPX-351 and had refractory disease later went on to receive HMA/Ven reinduction; 2 achieved CRi, 2 MLFS, 3 Refractory and 1 Death in Aplasia. 1 pt who initially received HMA/Ven with refractory disease went on to receive CPX-351. This pt was refractory to CPX-351. Conclusion: HMA/Ven and CPX-351 are effective frontline treatment options with similar response rates and survival outcomes in newly diagnosed adults with AML. Pts treated with CPX-351 were younger and more likely to proceed with allogeneic transplantation, in line with standard practice. Though there was heterogeneity in pt populations, age did not appear to affect outcomes. As the landscape for standard-of-care upfront treatment for AML continues to evolve, further studies are warranted to determine optimal therapy selection and sequencing. Figure 1 Figure 1. Disclosures Arnall: Novo Nordisk: Speakers Bureau. Symanowski: Carsgen: Consultancy; Immatics: Consultancy, Other: DSMB Member; Eli Lilly: Consultancy, Other: DSMB Member. Avalos: JUNO: Membership on an entity's Board of Directors or advisory committees. Copelan: Amgen: Consultancy. Grunwald: Cardinal Health: Consultancy; Daiichi Sankyo: Consultancy; Astellas: Consultancy; Agios: Consultancy; Janssen: Research Funding; PRIME: Other; Karius: Consultancy; Bristol Myers Squibb: Consultancy; AbbVie: Consultancy; Pfizer: Consultancy; Blueprint Medicines: Consultancy; Gilead: Consultancy; Incyte: Consultancy, Research Funding; Amgen: Consultancy; Med Learning Group: Other; Sierra Oncology: Consultancy; MDEdge: Other; PER: Other; Trovagene: Consultancy; Stemline: Consultancy. </jats:sec