Updates on therapy options for older AML & CLL patients

12 Sep 2016

More intense therapy and use of hypomethylating agents led to better survival for older patients with acute myelogenous leukemia (AML), according to a study.

Among 602 patients who had a median age of 77, treatment with hypomethylating agents led to a median overall survival of 13.3 months, and high-intensity therapy (daunorubicin/cytarabine or equivalent) led to a median overall survival of 9.5 months.

In contrast, low-intensity therapy (low-dose cytarabine or equivalent) led to a median overall survival of 5.9 months, and best supportive care was associated with a median survival of 2.5 months, Varun Dhulipala, MD, of Moffitt Cancer Center in Tampa, Fla., and colleagues reported. Pairwise comparisons showed that hypomethylating agents outperformed all three of the other treatment strategies. High-intensity therapy led to significantly better survival as compared with low-intensity therapy, and low-intensity therapy was no better than supportive care.

High-intensity therapy was the most commonly used strategy followed by supportive care, hypomethylating agents and low-intensity therapy. "Data from this study are being used to develop decision models to compare treatments in older patients with AML," the investigators stated.

Ibrutinib looks promising for older CLL patients

More than twice as many older patients with untreated chronic lymphocytic leukemia (CLL) responded to the Bruton's tyrosine kinase inhibitor ibrutinib (Imbruvica) versus chlorambucil, a phase 3 trial showed.

By independent review, ibrutinib led to an overall response rate of 86% as compared with 35.3% with chlorambucil, an alkylating agent commonly used to treat CLL in older patients, Jan Burger, MD, PhD, of the MD Anderson Cancer Center in Houston, and colleagues reported.

After a median follow-up of 18.4 months in the 269 trial participants, the median progression-free survival had yet to be reached in the ibrutinib group versus 18.9 months in the chlorambucil group, as determined by independent review. By investigator assessment, median progression-free survival was 15 months with chlorambucil and not-yet-reached with ibrutinib.

What about the adverse events?

The overall adverse event rate was similar between groups. The most common adverse events with ibrutinib were diarrhea (about 40%), fatigue (about 30%), and cough, nausea, and peripheral edema (about 20% each). Most of the adverse events were grade 1/2 severity.

Grade 4 neutropenia and grade 3 diarrhea occurred in around 5% of patients.


What’s the connection between ibrutinib and cardiac problems?

Eleven cases of ventricular arrhythmia and six cases of sudden cardiac death associated with ibrutinib treatment emerged from a review of institutional experience, clinical trial data, and the FDA Adverse Event Reporting System (FAERS).

Ibrutinib has a recognized arrhythmogenic potential, but an association with atrial fibrillation has attracted most attention to date, Benjamin Lampson, MD, of Dana-Farber Cancer Institute in Boston, and colleagues noted. After identifying four cases of ibrutinib-associated ventricular arrhythmia in Dana-Farber patients, investigators began looking for additional evidence of ventricular arrhythmias in published data from clinical trials and the FAERS.

The investigation showed that the ventricular events occurred after a median duration of 62 days of treatment with ibrutinib (range 6 to 366 days). In 12 of the 17 cases, patients had no prior history of cardiac events. In 10 cases, patients had extensive cardiac workups following the ventricular events, and nine of the workups failed to reveal any precipitating causes.

"These results suggest that the proarrhythmic potential of ibrutinib may extend beyond atrial fibrillation to the rare development of ventricular arrhythmias and sudden death," Lampson and colleagues concluded. "These adverse events should be actively investigated and reported in future trials of BTK inhibitors. "Clinicians should have a low threshold for additional cardiac workup in ibrutinib-treated patients reporting symptoms consistent with any arrhythmia, but particularly including ventricular arrhythmias."

Arzerra brings benefit to older CLL patients

The novel anti-CD20 antibody ofatumumab (Arzerra) led to objective responses in 75% of a cohort of older patients with CLL, investigators reported.

The 32 evaluable patients had a median age of 73, no prior treatment for CLL, and were considered unsuitable for enrollment in clinical trials, Lorenzo Falchi, MD, a 1-year clinical fellow at MD Anderson Cancer Center in Houston, and colleagues said.

In particular, the researchers reported that:

  • Monotherapy with ofatumumab led to objective responses in 24 patients, including complete responses in six patients and no evidence of minimal residual disease in three patients.
  • After a median follow-up of 25.3 months, 20 patients remained progression free and 32 of 34 patients remained alive.
  • No patient died on study.

No grade 4 adverse events occurred. Grade 3 adverse events consisted in diarrhea/nausea/vomiting in three patients and infusion-related reactions, infections, and pulmonary embolism in one patient each.

Source: MedPage Today

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