Dose Intensive Rituximab and High-Dose Methylprednisolone in Elderly or Unfit Patients with Relapsed Chronic Lymphocytic Leukemia
Abstract
:1. Introduction
2. Materials and Methods
2.1. Patients
2.2. Assessments and End Points
2.3. Study Treatment and Monitoring
2.4. Statistical Methods
2.5. Comparison of LT-CLL-001 and LT-CLL-2s Study Results
3. Results
3.1. Patient Characteristics
3.2. Response and Survival
3.3. Prognostic Factors for PFS and OS
3.4. Toxicity
3.5. Salvage Therapy
4. Discussion
5. Conclusions
Author Contributions
Funding
Conflicts of Interest
References
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Characteristic | N° of Patients | % |
---|---|---|
Number of patients | 25 | 100 |
Median age, years (range) ≥75 years | 73 (65–80) 9 | 36 |
Gender | ||
Male | 7 | 28 |
Female | 18 | 72 |
CIRS median (range) Median creatinine clearance (mL/min) | 5 (1–8) 54 | |
Rai stage | ||
I–II | 10 | 40 |
III–IV | 15 | 60 |
Bulky lymphadenopathy (>5 cm) | 12 | 48 |
B symptoms | 20 | 80 |
CD20 expression >80% | 18 | 72 |
B2 mikroglobulin >3.5 mg/L * | 23 | 96 |
ZAP 70 possitive | 16 | 64 |
IgHV unmutated | 17 | 68 |
Genetics | ||
17p deletion and/or TP53 deletion ** 11q deletion only *** Trisomy 12 only 13q deletion only | 5 3 2 7 | 20 12 8 28 |
Median no. of prior treatments (range) Median time from the last treatment, months (range) | 2 (1–3) 20 (0–153) | |
Fludarabine containing regimen Rituximab containing regimen | 7 3 | 28 10 |
Characteristics | PFS | OS | ||||
---|---|---|---|---|---|---|
HR | 95% CI | p | HR | 95% CI | p | |
Male gender | 0.840 | 0.319–2.208 | 0.723 | 1.117 | 0.333–3.750 | 0.858 |
p17del/TP53 mutation * | 6.314 | 1.905–20.930 | 0.003 | 3.285 | 0.952–11.337 | 0.060 |
Cycles No ≤4 vs. >4 | 1.060 | 0.448–2.507 | 0.895 | 0.344 | 0.074–1.598 | 0.174 |
Bulky disease > 5 cm | 2.847 | 1.140–7.114 | 0.025 | 2.081 | 0.656–6.607 | 0.214 |
ZAP expression | 3.850 | 1.343–11.039 | 0.012 | 1.392 | 0.418–4.641 | 0.590 |
IgVH mutation * | 0.168 | 0.051–0.548 | 0.003 | 0.319 | 0.070–1.466 | 0.142 |
CD38 expression ≥ 20% | 1.070 | 0.469–2.440 | 0.872 | 0.595 | 0.189–1.877 | 0.376 |
CD20 expression > 90% | 0.976 | 0.956–0.996 | 0.019 | 0.987 | 0.960–1.014 | 0.332 |
B2 microglobulin > 3.5 mg/L * | 1.303 | 1.045–1.625 | 0.019 | 1.228 | 0.999–1.510 | 0.051 |
Adverse Events | Grade I/II n (%) | Grade III/IV n (%) | Subjects with at Least One AE n |
---|---|---|---|
All reported | 106 (81) | 25 (19) | xxx |
Chills | 1 (9.4) | 1 | |
Cardiovascular disturbances | 17 (16.0) | 1 (4.0) | 15 |
Gastrointestinal disturbances | 4 (3.8) | 3 | |
Hematology | 4 (16.0) | 4 | |
Neutropenia | 2 (1.9) | * 16 (64.0) | 7 |
Infections | 11 (10.4) | 4 (16.0) | 8 |
Urticaria papulosa | 1 (9.4) | 1 | |
Lumbalgia subacuta | 3 (2.8) | 2 | |
Arthralgias/headache | 4 (3.8) | 4 | |
Cough | 3 (2.8) | 3 | |
Hyperuricemia | 1 (9.4) | 1 | |
Renal insufficiency | 2 (1.9) | 2 | |
Thrombosis | 2 (1.9) | 2 | |
Fever | 5 (4.7) | 3 | |
Edema | 5 (4.7) | 4 | |
Left femur cervical stress fracture | 1 (9.4) | 1 | |
Cognitive disturbance | 1 (9.4) | 1 | |
Hyperglycemia | 10 (9.4) | 1 (4.0) | 2 |
Hypokalemia | 30 (28.3) | 18 | |
Insomnia | 3 (2.8) | 3 |
Reference | Pts No | Age, Median | No of HDMP or DEXA Cycles (Days) | Total Dose of Rtx mg/m2 | Pt with 17pdel No. (%) | ORR/CR (%) | Median PFS, Months | Median OS, Months | AE III–V° |
---|---|---|---|---|---|---|---|---|---|
Castro et al. [4] | 14 | 62 | 3 (5) | 5250 | 1 (7) | 93/36 * | 15 | NR ** | One case of pneumonia |
Simkovic et al. *** [11] | 60 | 66 | 8 (8) | 3875 | 11 (23) | 75/3 | 8 | 25, 5 | 27% serious infections Treatment related mortality 10%, |
Doubek et al. [12] | 33 | 66 | 3/6 (8) | 8 (24) | 67/15 | 10 | 34 | III–IV° infections 21%, Treatment related mortality 12% | |
Pileckyte et al. [1] | 29 | 59 | 6 (5) | 3375 | 13 (44) | 62/0 | 12 | 31 | III–IV° infections 23% Treatment related mortality 10% |
Pileckyte et al. | 25 | 73 | 4/6 (3) | 4000 | 5 (20) | 28/0 | 11 | 68 | III–IV° infections 12% No treatment related deaths |
Byrd et al. [2] Ibrutinib | 195 | 67 | 63 (32) | 43/0 | At median follow-up of 9,4 months, median PFS not reached | At 12 months, the overall survival rate was 90% | ≥III° infections 24% Treatment related mortality 4% |
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Pileckyte, R.; Valceckiene, V.; Stoskus, M.; Matuzeviciene, R.; Sejoniene, J.; Zvirblis, T.; Griskevicius, L. Dose Intensive Rituximab and High-Dose Methylprednisolone in Elderly or Unfit Patients with Relapsed Chronic Lymphocytic Leukemia. Medicina 2019, 55, 719. https://doi.org/10.3390/medicina55110719
Pileckyte R, Valceckiene V, Stoskus M, Matuzeviciene R, Sejoniene J, Zvirblis T, Griskevicius L. Dose Intensive Rituximab and High-Dose Methylprednisolone in Elderly or Unfit Patients with Relapsed Chronic Lymphocytic Leukemia. Medicina. 2019; 55(11):719. https://doi.org/10.3390/medicina55110719
Chicago/Turabian StylePileckyte, Regina, Vilma Valceckiene, Mindaugas Stoskus, Reda Matuzeviciene, Jurgita Sejoniene, Tadas Zvirblis, and Laimonas Griskevicius. 2019. "Dose Intensive Rituximab and High-Dose Methylprednisolone in Elderly or Unfit Patients with Relapsed Chronic Lymphocytic Leukemia" Medicina 55, no. 11: 719. https://doi.org/10.3390/medicina55110719