PI3K/Anti-CD20 Therapy for Relapsed/Refractory CLL

Danielle M. Brander, MD: Another one of the options that we mentioned for patients with relapsed or refractory CLL [chronic lymphocytic leukemia] that is currently approved is the combination of idelalisib with or without rituximab. In a clinical trial led by Dr Sharman and colleagues, patients with relapsed or refractory CLL were randomized to either rituximab monotherapy, which was considered a standard of care at the time of the trial, versus rituximab with idelalisib. Idelalisib belongs to a family of compounds called PI3-kinase inhibitors. They’re often subclassified by the isoform that they target. For example, idelalisib is a delta isoform-specific inhibitor. This is important, as this isoform is particularly what is thought to be driving progression for patients with CLL and lymphoid malignancies.

For patients who are started on idelalisib and rituximab, as was done in the clinical trial, they are followed closely for both response and to monitor for toxicities, including LFT abnormalities or diarrhea that can occur early—within the first couple of weeks.

On the clinical trial as well as per the labeled prescribing information, one can learn how to follow patients, but also, importantly, how to treat patients should they develop any toxicities. This usually involves holding the drug. In the case of diarrhea, depending on the severity and concern for colitis and dehydration, you might also employ testing for other co-infections. If negative, it is recommended to use antimotility agents until the toxicities resolve to a lower grade. In the clinical trial, patients were also followed closely for other late onset of toxicities.

In the conclusion of the study and the follow-up of these patients randomized to either rituximab and placebo versus rituximab and idelalisib, there was a significant improvement in both progression-free survival and overall survival for the idelalisib/rituximab patients. This adds to the list of options for patients, outside of clinical trials.

Transcript edited for clarity.

Case: A 73-Year-Old Man With Relapsed Chronic Lymphocytic Leukemia

Initial Presentation

• A 73-year-old man presented to his PCP for an annual checkup; he complained of mild intermittent fatigue and occasional night sweats
• PMH: hypertension, medically controlled
• PE: palpable axillary and right-sided cervical lymphadenopathy
  
  

Clinical Work-up

• Labs: WBC 48,000, lymphocyte 72%, ANC 3700/mm3, Hb 9.4 g/dL, plt 100 x 109/L, LDH 240 U/L, Beta-2-microglobulin 4.1 mg/L
• FC CD 5+, CD23+, CD20+ monoclonal B-cell population
• FISH: normal for all CLL probe set tested, no evidence t11;14
• IGHV mutational status: unmutated
• Rai stage IV; Binet stage B
• ECOG PS 0

Treatment and Follow-up

• He was started on ibrutinib 420 mg PO qDay; symptoms improved and achieved stable disease resolution of lymphadenopathy
• After about 3 years he complained of increasing fatigue and decreased appetite, on PE return of palpable lymphadenopathy spleen was palpable ~4 cm below costal margin; creatinine clearance 56 mL/min