Clinical experience with the BCL2-inhibitor venetoclax in combination therapy for relapsed and refractory acute myeloid leukemia and related myeloid malignancies.

INTRODUCTION: Venetoclax (VEN), a selective BCL2 inhibitor, has single-agent activity in relapsed and refractory (R/R) acute myeloid leukemia (AML), and efficacy in lower intensity combinations for treatment-naïve elderly AML patients. VEN treatment combinations in R/R AML have not been previously reported. METHODS: All R/R myeloid patients (including AML, myelodysplastic syndrome (MDS), and blastic plasmacytoid dendritic cell neoplasm (BPDCN)) treated with VEN combinations in the salvage setting were reviewed. RESULTS: Forty-three patients with median age 68 (range, 25-83) were treated for AML (91%), MDS (5%), or BPDCN (5%). Most (n = 36, 84%) were ≥ salvage-2 treatment status, including prior hypomethylating agent (HMA) in 77%. In combination with VEN, most patients received HMA therapy (n = 31, 72%); eight (19%) received low-dose cytarabine (LDAC). Patients received a median of 2 treatment cycles (range, 1-4). Objective response was observed in 9 (21%) patients, including 2 complete responses (CR), 3 CRi, and 4 morphologic leukemia-free state (MLFS). Median survival was 3.0 months (range, 0.5-8.0), and estimated 6-month survival was 24%. Responses were observed in five (24%) of 21 patients with intermediate-risk cytogenetics, 3 (27%) of 11 IDH1/2-mutant, and 4 (50%) of 8 RUNX1-mutated patients. Two (20%) of 10 TP53-mutated patients responded; both had concurrent RUNX1 mutations. Of the 3 (15%) responding patients with adverse cytogenetics, all had concurrent RUNX1 mutations. CONCLUSION: Low-intensity chemotherapy, including HMAs or LDAC, in combination with VEN is a viable salvage option, even in multiply relapsed/refractory patients with AML, MDS, and BPDCN. Notable responses were identified in patients with diploid/intermediate cytogenetics, RUNX1, and/or IDH1/2 mutations.

Direct Clinical Pharmacist-Patient Telephone Follow-Up: A Focus on GI Medical Oncology Symptom Management.

PURPOSE: GI medical oncology care presents unique medication challenges. Here, we captured our clinical pharmacy specialists' (CPSs) involvement in patients with GI cancers starting cycle 1 of a new treatment. METHODS: Our quality initiative was performed in three stages (preintervention, intervention, and postintervention). Preintervention: retrospective baseline data collection from May to December 2019. Intervention: one-time telephone encounters were conducted by a CPS between March 15 and June 11, 2021. The primary objective of the quality improvement initiative was to increase patient interaction with a CPS to 80%. Postintervention: data collection to review the impact of CPS telephone encounters. RESULTS: Preintervention: we reviewed the electronic health records of 262 patients. Sixty nine percent of patients reported at least one adverse event (AE; range 1-6 AEs) at the first physician follow-up after treatment start. Most reported AEs (78%) were considered modifiable within the scope of CPS practice. Postintervention: during the intervention, 92% of patients (n = 389) received a telehealth encounter with the CPS. At the encounter, 315 patients (81%) reported at least one AE. CPS provided recommendations and/or additional education for 88% of reported AEs. Medication lists required correction 75% of the time. The median time for CPS encounters (including documentation) was 40 minutes. CONCLUSION: During a 3-month period, this quality improvement initiative successfully provided an early CPS-based telehealth intervention to identify and make initial recommendations for management of AEs for patients on cycle 1 of systemic therapy for GI cancer.

Idelalisib for treatment of B-cell malignancies.

PURPOSE: The pharmacology, pharmacokinetics, clinical efficacy, safety and tolerability, dosing and administration, and place in therapy of idelalisib, a targeted therapy for certain types of non-Hodgkin's lymphoma (NHL), are reviewed. SUMMARY: Historically, conventional cancer chemotherapy agents were recommended for the management of progressive lymphomas requiring systemic treatment; in recent years, however, emerging targeted therapies have altered the landscape of lymphoma treatment. Idelalisib, a novel oral phosphatidylinositol 3-kinase (PI3K) inhibitor, disrupts downstream signaling pathways involved in cancer cell growth and survival. Inhibition of PI3K has been demonstrated to produce durable treatment responses and improved survival outcomes in clinical trials involving patients with indolent forms of NHL. Idelalisib is indicated for use in combination with rituximab for treatment of relapsed chronic lymphocytic leukemia (CLL) and as monotherapy for relapsed small lymphocytic leukemia and follicular lymphoma after the failure of at least two systemic treatments. The recommended dosage of idelalisib is 150 mg orally twice daily; the medication can be taken without regard to mealtimes. The most common adverse effects of idelalisib include diarrhea, nausea, fatigue, cough, and pyrexia. Severe hepatotoxicity and gastrointestinal toxicities, including colitis and intestinal perforation, have also been reported in association with idelalisib use. Ongoing clinical studies are exploring the potential for expanded use of idelalisib in the management of other B-cell malignancies. CONCLUSION: Idelalisib is a well-tolerated and effective treatment for patients with relapsed or refractory CLL or indolent NHL, providing a novel targeted therapeutic option for the management of these hematologic malignancies.

Which tyrosine-kinase inhibitor to use first in chronic phase chronic myelogenous leukemia?

INTRODUCTION: Chronic myelogenous leukemia (CML) is a clonal myeloproliferative disorder distinctly characterized by the presence of the Philadelphia chromosome, which results from a reciprocal translocation between chromosomes 9 and 22 [t(9;22)]. The resulting translocation leads to the development of the BCR-ABL1 oncogene, a constitutively active fusion protein, which leads to uncontrolled cell proliferation and reduced apoptosis and has a clear association with driving the malignant activity of CML cells. AREAS COVERED: Given that the BCR-ABL1 oncogene is a known key cause of CML, it has led to the development of numerous small molecule tyrosine-kinase inhibitors (TKIs), which target the specific oncogene mutation in CML. Presently, there are three FDA-approved TKI agents, imatinib, dasatinib and nilotinib, for the treatment of frontline CML. Herein, we review the frontline options for the management of patients with CML and how to best choose these agents. EXPERT OPINION: Imatinib, dasatinib and nilotinib are all effective at yielding hematological, molecular and cytogenetic responses in patients with newly diagnosed CML. Frontline therapy may depend on physician experience, patient age and ability to tolerate therapy, and with the lack of data comparing all three agents alongside each other, imatinib, dasatinib, or nilotinib may all be suitable frontline choices.