Page 160 - Haematologica-April 2018

A.-S. Michallet et al.
Table 4. Summary of AEs (safety population).
Patients, n (%)
Blood and lymphatic system disorders Neutropenia
Leukopenia
Anemia
Thrombocytopenia
Lymphopenia Gastrointestinal disorders
Nausea Diarrhea Constipation
General disorders and administrative site conditions Pyrexia
Asthenia
Skin and subcutaneous tissue disorders
Rash
Most common grade ≥3 AEsb
Blood and lymphatic system disorders Neutropenia
Leukopenia
Anemia
Lymphopenia Thrombocytopenia Febrile neutropenia
Most common SAEsb Infections and infestations
Pneumonia
Blood and lymphatic system disorders
Febrile neutropenia
R-B (N=177)
173 (98)
132 (75) 73 (41)
133 (75) 99 (56) 42 (24) 41 (23) 37 (21) 30 (17) 99 (56) 53 (30) 30 (17) 28 (16) 93 (53) 37 (21) 29 (16) 63 (36) 29 (16)
99 (56) 76 (43) 29 (16) 18 (10) 17 (10) 17 (10) 12 (7)
33 (19) 8 (5) 25 (14) 11 (6)
R-Clb (N=178)
173 (97)
113 (64) 56 (32)
113 (64) 88 (49) 31 (17) 27 (15) 44 (25) 21 (12) 90 (51) 46 (26) 22 (12) 23 (13) 87 (49) 17 (10) 34 (19) 40 (23) 9 (5)
84 (47) 65 (37) 15 (8) 12 (7) 10 (6) 16 (9) 7 (4)
15 (8) 2 (1) 15 (8) 7 (4)
All-grade AEs
Grade ≥3 AEs
SAEs
Most common all-grade AEsa
704
aPreferred terms with incidence of ≥15% in either study arm. bPreferred terms with incidence of ≥5% in either study arm. Non-serious AEs were reported until 28 days after the end of the last treatment cycle. SAEs unrelated to study treatment were reported until six months after the end of treatment or until the start of new anti- chronic lymphocytic leukemia treatment.Treatment-related SAEs were to be reported indefinitely. AE: adverse event; R-B: rituximab plus bendamustine; R-Clb: rituximab plus chlorambucil; SAE: seri- ous adverse event.
infections and infestations. Few patients in either arm dis- continued therapy due to AEs. Treatment withdrawal due to AEs was reported for 18% of patients receiving 1L R-B and 12% receiving R-Clb.
As previously noted, the results of the CLL11 study show that, in unfit CLL patients, G-Clb was associated with higher response rates and longer PFS than R-Clb, with more frequent MRD eradication and an acceptable toxicity profile.10 In addition, current guidelines, (European Society for Medical Oncology and National Comprehensive Cancer Network), recommend Clb in combination with an anti-CD20 antibody as standard 1L therapy in unfit CLL patients.20,21 However, in MABLE and previous studies, R-B was associated with a good response rate and improved PFS compared with R-Clb. Currently, evidence to guide the choice between R-B and G-Clb in 1L unfit patients with CLL is limited, although a recent meta-
analysis of PFS and OS results in five studies showed a trend towards better efficacy for G-Clb than R-B;22 how- ever, the difference was not significant despite a signifi- cant difference between G-Clb and other comparators such as R-Clb, Ofa-Clb, Clb, and fludarabine. A random- ized trial comparing these combinations could resolve this question.
Some limitations of our study should be acknowledged. Since we relied only on investigator assessments of tumor response to evaluate efficacy, and did not include assess- ments by an independent review committee, this might have introduced a potential bias in the efficacy results. Comparison of our results with those of other studies in CLL patients is potentially complicated because the selec- tion of patients based on fitness was based on a judgment made by the investigator that the patients were not eligi- ble for fludarabine, according to a set of pre-defined crite-
haematologica | 2018; 103(4)