Ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (iFCG) regimen for chronic lymphocytic leukemia (CLL) with genetic abnormalities

This study aimed to investigate the outcomes for patients with chronic lymphocytic leukemia (CLL), with genetic abnormalities (mutated IGHV) and without del(17p)/TP53 mutation, who were treated with the iFCG (ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab) regimen. 

This study concluded that this treatment regimen is effective for these patients.  

Chemoimmunotherapy combines chemotherapy with immunotherapy. Chemotherapy uses drugs to kill or slow the growth of cancer cells. Immunotherapy uses treatments to stimulate the immune system or restore its ability to fight cancer. Combined fludarabine (Fludara), cyclophosphamide, (Cytoxan) and rituximab (Rituxan) has been an effective treatment for patients with chronic lymphocytic leukemia (CLL). This regimen has been shown to work particularly well in patients who have an abnormal IGHV gene. 

Obinutuzumab (Gazyva) is an immunotherapy that works similarly to rituximab. Ibrutinib (Imbruvica) is a targeted therapy commonly used for the treatment of CLL. It was unknown if a combination of ibrutinib, fludarabine, cyclophosphamide, and obinutuzumab (iFCG) would be effective in CLL patients with mutated IGHV and without del(17p)/TP53 mutation.  

This study involved 45 patients with previously untreated CLL with mutated IGHV and absence of del(17p)/TP53 mutation. Patients were treated with iFCG for three cycles. Patients who achieved complete remission (CR) received 9 cycles of ibrutinib with 3 cycles of obinutuzumab. All other patients received 9 additional cycles of ibrutinib and obinutuzumab. Patients who achieved undetectable minimal residual disease (U-MRD) after cycle 12 stopped all treatment. MRD is the small number of cancer cells that remain after treatment. U-MRD is when no cancer cells can be found. Patients were followed up for an average of 41.3 months. 

After three cycles, 38% of patients achieved CR and 87% of patients achieved U-MRD in the bone marrow. After cycle 12, 67% of patients achieved CR and 91% of patients achieved U-MRD. 98% of patients achieved marrow U-MRD as the best response.  

No patient had CLL progression. 98% of patients were alive and progression-free after 3 years. After an average of 24.9 months after stopping ibrutinib treatment, 3 patients had CLL recurrence in the blood, without disease progression.  

58% of patients experienced severe low blood cell counts and 40% of patients experienced severe low platelet counts.

This study concluded that iFCG with only three cycles of chemotherapy is an effective, time-limited regimen for patients with CLL with mutated IGHV and without del(17p)/TP53 mutation.  

This study had a very small number of participants. No comparison treatment group was used. This study was funded by Pharmacyclics LLC and Genentech, the manufacturers of ibrutinib and obinutuzumab.