Management of adverse events associated with idelalisib treatment in chronic lymphocytic leukemia and follicular lymphoma: A multidisciplinary position paper

Abstract

The introduction of new therapeutic agents in chronic lymphocytic leukemia (CLL) and follicular lymphoma (FL), including the new kinase inhibitor idelalisib, has changed the therapeutic landscape of these diseases. However, the use of idelalisib is associated with a peculiar profile of side effects, which require an optimization of the current approach to prophylaxis and supportive treatment. Moving from the recognition that the abovementioned issue represents an unmet need in CLL and FL, a multidisciplinary panel of experts was convened to produce a consensus document aiming to provide practical recommendations for the management of the side effects during idelalisib therapy for CLL and FL. The present publication represents a consensus document from a series of meetings held during 2017. The Panel generated clinical key questions using the criterion of clinical relevance through a Delphi process and explored 4 domains, ie, diarrhea/colitis, transaminitis, pneumonitis, and infectious complications. Using the consensus method, the Panel was able to shape recommendations which may assist hematologist to minimize adverse events and guarantee adherence to treatment in patients with CLL and FL candidate to receive idelalisib.

Keywords: adverse events; chronic lymphocytic leukemia; follicular lymphoma; idelalisib.

Figure 1

The issue of diarrhea/colitis: assessment of patients assigned to treatment with idelalisib ± rituximab as first option

Figure 2

Management of idelalisib‐induced diarrhea. (*grade 1 = stool increase <4/day over baseline; grade 2 = stool increase 4‐6; grade 3 = stool increase ≥7, hospitalization required; grade 4 = life threatening; **always if bleeding)

Figure 3

The issue of transaminitis: assessment of patients assigned to treatment with idelalisib ± rituximab as first option. (UNL, upper normal limit; DAA, directly acting antivirals; *>5 UNL because of a histologically proved CLL‐dependent or FL‐dependent liver disease)

Figure 4

Management of transaminitis. (UNL, upper normal limit; ALT, alanine aminostransferase)

Figure 5

The issue of pneumonitis: management algorithm for patients assigned to treatment with idelalisib ± rituximab as first option (UNL, upper normal limit; PB, peripheral blood; COPD, chronic obstructive pulmonary disorder; CRP, C‐reactive protein; BAL, bronchoalveolar lavage; *>5 UNL because of a histologically proved CLL‐dependent or FL‐dependent liver disease; DAA, directly acting antivirals)

Figure 6

The issue of infectious complications: management algorithm for patients assigned to treatment with idelalisib ± rituximab as first option. (UNL, upper normal limit; PB, peripheral blood; BAL, bronchoalveolar lavage; GE, gastroenterologist; TB, tubercolosis; *>5 UNL because of a histologically proved CLL‐dependent or FL‐dependent liver disease; DAA, directly acting antivirals)

Figure 7

Algorithm for tuberculosis screening. (*any symptoms of TB include any 1 of cough, hemoptysis, fever, night sweats, weight loss, chest pain, shortness of breath, fatigue; TST, tubercolin skin test; IGRA, interferon‐gamma release assays)