Haematology

The study shows that the Food and Drug Administration approve venetoclax (VENCLEXTA, AbbVie Inc. and Genentech Inc.) for adult patients with chronic lymphocytic leukemia (CLL)  ;or small lymphocytic lymphoma (SLL). Therefore  Approval was based on CLL14 (NCT02242942); a randomized (1:1), multicenter, open label; actively controlled trial of venetoclax in combination with obinutuzumab (VEN+G) versus obinutuzumab in combination with chlorambucil ; (GClb) in 432 patients with previously untreated CLL with coexisting medical conditions.

Trial of venetoclax in combination

Venetoclax (VENCLEXTA) has been approved to treat adult patients with chronic lymphocytic leukemia ; (CLL) or small lymphocytic lymphoma; the U.S. Food and Drug Administration announced yesterday.Data from CLL14, a randomized; multicenter, open-label, actively controlled trial, provided the basis for approval.

CLL14 involved 432 patients with previously untreate CLL and coexisting medical conditions who are randomly assigned to venetoclax plus obinutuzumab (VEN+G) ; or obinutuzumab plus chlorambucil (GClb). The researchers observed a statistically significant improvement in progression-free survival for patients who received VEN+G compared with those who received GClb (hazard ratio, 0.33).

Coexisting medical conditions

Overall response was 85% in patients who received VEN+G and 71% in those who received GClb. VENCLEXTA is available in 10-, 50-, and 100-mg tablets. Dosing begins with a five-week ramp-up, and the FDA advises clinicians to consult the manufacturer prescribing information for the full ramp-up schedule.

When administered with obinutuzumab, with rituximab, or as monotherapy, the most commonly reported adverse reactions of venetoclax included neutropenia, thrombocytopenia, anemia, diarrhea, nausea; upper respiratory tract infection, cough, musculoskeletal pain, fatigue, and edema. The manufacturer prescribing information also warns of the potential risk for tumor lysis syndrome during the ramp-up phase and directs clinicians to advise patients of the signs and symptoms.

The major efficacy outcome was progression-free survival (PFS) ; assessed by an independent review committee. The trial demonstrated a statistically significant improvement in PFS for patients who received VEN+G compared with those who received GClb (HR 0.33; 95% CI: 0.22, 0.51; p<0.0001). Median PFS was not reached in either arm after a median follow-up duration of 28 months.

Significant improvement

The overall response rate is 85% in VEN+G arm compare to 71% in GClb arm, p=0.0007. The trial also demonstrated statistically significant improvements in rates of minimal residual disease negativity ; (less than one CLL cell per 104 leukocytes) in bone marrow and peripheral blood.

Overall survival data were not mature at this analysis.In CLL/SLL; the most common adverse reactions (≥ 20%) for venetoclax when administered with obinutuzumab, rituximab; or as monotherapy were neutropenia, thrombocytopenia, anemia, diarrhea, nausea; upper respiratory tract infection, cough, musculoskeletal pain; fatigue, and edema.FDA used the Real-Time Oncology Review and Assessment Aid Pilot Program for this application and granted priority review as well as orphan drug and breakthrough therapy designations.