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ASCO 2019: Pick #4 Duvelisib: Effects of Dose modifications in relapsed/ refractory (R/R) chronic lymphocytic leukemia (CLL)

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Dr. Brian Koffman, the Executive Vice President (EVP) and Chief Medical Officer (CMO) of the CLL Society, counts down his top ten CLL related abstract from ASCO or the American Society of Clinical Oncology Annual Meeting held May 31 – June 4, 2019, Chicago, IL.

#4

Effect of dose modifications on response to duvelisib in patients with relapsed/refractory (R/R) CLL/SLL in the DUO trial.

There are two approved types of medications that block B cells and lead to excellent control of CLL.

The best known are ibrutinib (Ibrutinib) and acalabrutinib (Calquence) that inhibit the B cell receptor (BCR) downstream by inhibiting BTK.

Idelalisib (Zydelig) and duvelisib (Copiktra) also block the BCR, but they do it by inhibiting the PI3K pathway.

While both BTK and PI3K inhibitors are very effective in controlling CLL, the BTK drugs tend to used much more as they are indicated in both frontline and R/R chronic lymphocytic leukemia and they tend to have a more manageable side effect profile.

In comparison, both PI3K drugs are approved only for R/R disease and may have more frequent serious side effects that require holding the medication or lowering the dose.

This trial led by Dr. Ian Flinn, from Tennessee Oncology and the Sarah Cannon Research Institute in Nashville, TN, examined whether such dose adjustments of the newer approved PI3K Inhibitor, duvelisib effected its clinical benefits.

Takeaways:

  • Of the patients treated for slightly less than a year with duvelisib, a full 80% reported a dose interruption (DI) and 27% required a dose reduction (DR).
  • The most common reason for DI was diarrhea in 23%, followed by a low neutrophil count in 12% and pneumonia or colitis in 11% each.
  • Response was improved or maintained in 84% patients evaluated for response who had ≥ 1 DI for > 1 week and 82% where it had held > 2 weeks, after which they were able to restart the medicine for at least another 3 weeks.
  • Progression free survival (PFS) was similar in patients with DI and those without DI for both > 1 week or > 2 weeks within the first 3 months.
  • Less than 10% of patients stopped the medication due to adverse events.

Conclusions:

As the former surgeon general, Dr. Koop famously said, “Drugs don’t work in patients who don’t take them.” Turns out that if we interrupt the dose or reduce, but are able to stay on, at least in the case of duvelisb it still does the job. That was not a “given” and good on Dr. Flnn and the other investigators for this important research.

It is especially good news for those taking duvelisib because most patients did need to hold the medicine or reduce the dose due to side effects, and now they can be confident that they will still get the benefits and be able to safely tolerate their medication.

This is also good news for all CLL patients as it makes another potent medication easier to use should they need it.

One caveat: I caution that because this is true for duvelisib, one should not assume the same is the case for any other drugs unless one checks whether or not similar research has been done for the medication in question.

Here is the link to my video review of the ASCO abstract:

Here is the link to the ASCO abstract itself: Effect of dose modifications on response to duvelisib in patients with relapsed/refractory (R/R) CLL/SLL in the DUO trial.

Thanks for your attention.

Stay strong. Be flexible.

We are all in this together

Brian