Contributions
Abstract: PB1869
Type: Publication Only
Background
BTK and BCL2 inhibitors have changed the treatment paradigms of high risk and/or elderly patients with chronic lymphocytic leukemia (CLL), but long term efficacy and toxicity are still unknown and the costs are relevant. Rituximab (RTX) and high dose methylprednisolone (HDMP) can be an effective and safe treatment option for relapsed CLL. Here, we present the long term results of two phase II studies of HDMP and RTX combination given in different schedules.
Aims
LT-CLL-001: to evaluate the efficacy and safety of HDMP and RTX in relapsed (R) high risk CLL patients.LT-CLL-2S: to evaluate the efficacy and safety of HDMP and RTX in relapsed elderly or unfit CLL patients
Methods
In LT-CLL-001 R CLL patients with high risk features (17p del, TP53 mut, 11q del and/or trisomy 12 or fludarabine refractory) were included. The treatment schedule was described elswere.¹In LT-CLL-2S study, relapsed patients with CIRS > 6 and / or ≥ 65 years were included. HDMP was administered at 1 g/m2 iv daily for 3 days of each course for 4 or 6 courses. RTX was administered at 1000 mg/m2 on day 1 of each course for 4 courses. Treatment cycles were repeated every 3 weeks.
Results
29 patients were enrolled in LT-CLL-001. Demographic data have been described elswere¹. The median observation time was 31 (1-76 ) month. The follow up for alive patients was 66.5 (60-76) months. Overall response rate (ORR) was 62%, all partial remissions (PR). The median progression free survival (PFS) and overall survival (OS) were 12 and 31 months. Five-year OS was 21% for all the patients; for patients with 17p deletion/TP53 mutation 3-year OS was 38%, 5-year OS was 8%. Grade III - Vᵒ infections were observed in 2% of all AEs.3 patients died during treatment phase. There were 3 cases (10.3%) of secondary malignancies: 1 Richter transformation, 1 polycythaemia vera and 1 breast cancer.25 patients were included in LT-CLL-2S. The median age was 73 years (range 65-80), 6 (26%) had 17pdel/TP53 mutation, 3 (12%) had 11q del. 9 patients were given > 4 courses 16 patients were given ≤ 4 courses. ORR was 28%, all PR, mainly due to residual lymphadenopathy. All 18 patients with B symptoms had their symptoms resolved. Significant improvement in anemia (p<0,001) was noted. The median follow-up was 44 (11-69) months. The median PFS was 11 months (range 10-12). Median OS was 68 (62-74) months. No difference in ORR or PFS was noted between patients who received ≤ 4 or > 4 courses, but a tendency for better OS was observed for the patients with more treatment (36 months versus not reached, p=0.062). AE were mainly I-IIº (82%), no deaths occurred during treatment.After their respective study, the relapsed patients with treatment indications recieved ibrutinib in notable difference between the studies: one (5%) out of 20 LT-CLL-001 patients compared to 7 (32 %) out of 22 LT-CLL-2S patients.
Conclusion
Lower ORR was observed in LT-CLL-2S compared to LT-CLL-001 mostly because of residual lymphadenopathy. However, median PFS between the studies were similar and toxicity of LT-CLL-2S was lower.The different ORR in two studies could be explained by the higher dose of HDMP in LT-CLL-001. The longer median OS in LT-CLL-2S could be explained by lower number of high risk patients and the availability for BTK inhibitors as salvage therapy. HDMP and RTX combination can still be applied in some relapsed high risk and elderly or unfit CLL patients without the significant risk of concomitant diseases exacerbation if new therapies are contraindicated or unavailable.
Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical
Keyword(s): Rituximab
Abstract: PB1869
Type: Publication Only
Background
BTK and BCL2 inhibitors have changed the treatment paradigms of high risk and/or elderly patients with chronic lymphocytic leukemia (CLL), but long term efficacy and toxicity are still unknown and the costs are relevant. Rituximab (RTX) and high dose methylprednisolone (HDMP) can be an effective and safe treatment option for relapsed CLL. Here, we present the long term results of two phase II studies of HDMP and RTX combination given in different schedules.
Aims
LT-CLL-001: to evaluate the efficacy and safety of HDMP and RTX in relapsed (R) high risk CLL patients.LT-CLL-2S: to evaluate the efficacy and safety of HDMP and RTX in relapsed elderly or unfit CLL patients
Methods
In LT-CLL-001 R CLL patients with high risk features (17p del, TP53 mut, 11q del and/or trisomy 12 or fludarabine refractory) were included. The treatment schedule was described elswere.¹In LT-CLL-2S study, relapsed patients with CIRS > 6 and / or ≥ 65 years were included. HDMP was administered at 1 g/m2 iv daily for 3 days of each course for 4 or 6 courses. RTX was administered at 1000 mg/m2 on day 1 of each course for 4 courses. Treatment cycles were repeated every 3 weeks.
Results
29 patients were enrolled in LT-CLL-001. Demographic data have been described elswere¹. The median observation time was 31 (1-76 ) month. The follow up for alive patients was 66.5 (60-76) months. Overall response rate (ORR) was 62%, all partial remissions (PR). The median progression free survival (PFS) and overall survival (OS) were 12 and 31 months. Five-year OS was 21% for all the patients; for patients with 17p deletion/TP53 mutation 3-year OS was 38%, 5-year OS was 8%. Grade III - Vᵒ infections were observed in 2% of all AEs.3 patients died during treatment phase. There were 3 cases (10.3%) of secondary malignancies: 1 Richter transformation, 1 polycythaemia vera and 1 breast cancer.25 patients were included in LT-CLL-2S. The median age was 73 years (range 65-80), 6 (26%) had 17pdel/TP53 mutation, 3 (12%) had 11q del. 9 patients were given > 4 courses 16 patients were given ≤ 4 courses. ORR was 28%, all PR, mainly due to residual lymphadenopathy. All 18 patients with B symptoms had their symptoms resolved. Significant improvement in anemia (p<0,001) was noted. The median follow-up was 44 (11-69) months. The median PFS was 11 months (range 10-12). Median OS was 68 (62-74) months. No difference in ORR or PFS was noted between patients who received ≤ 4 or > 4 courses, but a tendency for better OS was observed for the patients with more treatment (36 months versus not reached, p=0.062). AE were mainly I-IIº (82%), no deaths occurred during treatment.After their respective study, the relapsed patients with treatment indications recieved ibrutinib in notable difference between the studies: one (5%) out of 20 LT-CLL-001 patients compared to 7 (32 %) out of 22 LT-CLL-2S patients.
Conclusion
Lower ORR was observed in LT-CLL-2S compared to LT-CLL-001 mostly because of residual lymphadenopathy. However, median PFS between the studies were similar and toxicity of LT-CLL-2S was lower.The different ORR in two studies could be explained by the higher dose of HDMP in LT-CLL-001. The longer median OS in LT-CLL-2S could be explained by lower number of high risk patients and the availability for BTK inhibitors as salvage therapy. HDMP and RTX combination can still be applied in some relapsed high risk and elderly or unfit CLL patients without the significant risk of concomitant diseases exacerbation if new therapies are contraindicated or unavailable.
Session topic: 6. Chronic lymphocytic leukemia and related disorders - Clinical
Keyword(s): Rituximab