LEUKEMIA

3-drug therapy shows promise

A new three-combination drug therapy is highly active and well tolerated in patients with high-risk chronic lymphocytic leukemia (CLL) in an abstract presented at the 64th Annual American Society of Hematology Meeting.

The combination consists of venetoclax (V), obinutuzumab (O), and acalabrutinib (A).

The study, a continuation of a study whose initial results were published in 2021, enrolled 68 treatment-naive patients with CLL with any genetic risk profile.

About 83% of patients who were tumor protein 53-aberrant achieved bone marrow undetectable minimal residual disease after 15 months of treatment. Furthermore, the researchers observed low rates of cardiac and infectious toxicity. All grade hematologic toxicity included neutropenia, thrombocytopenia, and anemia. Nonhematologic toxicity included headache, fatigue, ecchymoses, nausea, diarrhea, infusion-related reactions, hypertension, increased alanine transaminase, arthralgia, and infection (one case of COVID-19 pneumonia).

About 3% of patients had atrial fibrillation, 21% required dose reduction of either only A (4%), V (9%), or both (7%).

Reference: Ryan C. Updated results from a multicenter, phase 2 study of acalabrutinib, venetoclax, obinutuzumab (AVO) in a population of previously untreated patients with CLL enriched for high-risk disease. American Society of Hematology. 2022. https://ash.confex.com/ash/2022/webprogram/Paper168003.html. Accessed December 15, 2022.

ALTERNATIVE MEDICINE

More results needed for use in heart failure

The American Heart Association (AHA) has released a position statement on complementary and alternative medicine (CAM).

Though the use of CAM is growing, with some studies returning indications of at least some clinical benefit, the AHA says that more research and randomized controlled trials are still warranted. Furthermore, they stress that some CAM can worsen conditions, such as heart failure, or interact with medications commonly used by adults with heart failure.

The authors write that a multidisciplinary team with pharmacist involvement can improve drug therapy management and safety in patients with heart failure who use CAM. They write that healthcare professionals may perform causality assessment of potentially CAM-related adverse reactions and interactions to determine the likelihood of CAM-induced harm; report CAM-related adverse reactions to health authorities even if the casualty assessment remains unclear; and routinely evaluate CAM in heart-failure management and discourage continued use if adverse effects, drug interactions, or both are known to cause harm.

Reference: Chow SL, Bozkurt B, Baker WL, et al. Complementary and alternative medicines in the management of heart failure: a scientific statement from the American Heart Association. Circulation. [e-pub Dec. 8, 2022]

PANCREATIC CANCER

Therapy increases survival

Adjuvant chemotherapy (AC) following multiagent neoadjuvant chemotherapy (NAC) in patients with pancreatic ductal adenocarcinoma (PDAC) is associated with significant survival benefit compared with that in patients who did not receive AC in a paper published in JAMA Oncology.

Researchers conducted a retrospective, matched-cohort study using data from the National Cancer Database. To be included, patients had to be at least 18 years of age, received multiagent NAC followed by surgical resection, and had available records of the pathologic findings. Patients were excluded if they had clinical or pathologic stage IV disease or died within 90 days of their surgery.

After being matched by propensity score according to demographic and pathologic characteristics, 888 patients remained: 444 in both the AC and non-AC group.

A Multivariable Cox regression model adjusted for all covariates revealed an association between AC and improved survival. AC was significantly associated with better overall survival (26.6 versus 21.2 months). However, the authors note that this benefit varied by age, pathologic T category, and tumor differentiation.

AC was associated with better survival in patients with any pathologic N category and positive margin status.

Reference: Sugawara T, Rodriguez Franco S, Sherman S, et al. Association of adjuvant chemotherapy in patients with resected pancreatic adenocarcinoma after multiagent neoadjuvant chemotherapy. JAMA Oncol. [e-pub Dec. 8, 2022]

KIDNEY DISEASE

Treatment may extend event-free survival

Treatment with a combination of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) and sodium-glucose cotransporter-2 (SGLT2) inhibitors in patients with albuminuric chronic kidney disease (CKD) without diabetes may substantially increase kidney failure-free survival, according to authors of a paper published in the Clinical Journal of the American Society of Nephrology.

Authors collected trial-level estimates of the effect of treatment with ACEIs/ARBs (ramipril/benazepril) and SGLT2 inhibitors (dapagliflozin) compared with placebo. From this, they estimated the treatment effect of combination therapy to the active treatment group of patients with albuminuric CKD without diabetes participating in the Dapagliflozin and Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) trial and projected event-free and overall survival for those treated and not treated with combination therapy.

Overall, the authors estimate the hazard ratio comparing combination therapy with ACEIs/ARBs and SGLT2 inhibitors versus no treatment was 0.35.

A 50-year-old patient, until the age of 75, can extend event-free survival for 17.0 years with the combination therapy and 9.6 years with no treatment. This represents a gain of about 7.4 years with combination therapy. Even if said patient had lower adherence, event-free survival could range from 5.3 to 5.8 years.

Reference: Vart P, Vaduganathan M, Jongs N, et al. Estimated lifetime benefit of combined raas and SGLT2 inhibitor therapy in patients with albuminuric CKD without diabetes. Clin J Am Soc Nephrol. 2022;17(12):1754-1762. doi:10.2215/cjn.08900722.

MELANOMA

New cell therapy enhances survival

Tumor-infiltrated lymphocytes (TILs) resulted in significantly longer progression-free survival than in patients who received ipilimumab.

In a phase 3, multicenter, open-label trial, 168 patients with advanced melanoma were randomly assigned to receive either TILs or ipilimumab; 84 were assigned to each. TILs were preceded by nonmyeloablative, lymphodepleting chemotherapy (cyclophosphamide plus fludarabine) and followed by high-dose interleukin-2.

The median progression-free survival of those receiving TILs was 7.2 months, whereas progression-free survival in those receiving ipilimumab was 3.1 months. The median overall survival rate was 25.8 months for those receiving TILs and 18.9 months for those receiving ipilimumab.

Adverse events associated with treatment occurred in all patients receiving TILs. These were mainly chemotherapy-related myelosuppression. In the group receiving ipilimumab, 57% had experienced similar adverse events.

Reference: Rohaan MW, Borch TH, van den Berg JH, et al. Tumor-infiltrating lymphocyte therapy or ipilimumab in advanced melanoma. N Engl J Med. 2022;387(23):2113-2125. doi:10.1056/nejmoa2210233.