A Multi-Center, Open-Label Study To Evaluate the Safety and Efficacy of Pentostatin, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated or Treated Bulky Stage II or Stage III or IV, Low-Grade B-Cell NHL.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4750-4750
Author(s):  
Raul R. Mena ◽  
Neal P. Christiansen ◽  
David W. Nyman ◽  
Yudhishtra Markan ◽  
Naveed M. Chowhan
Keyword(s):  
Combination Therapy ◽  
B Cell ◽  
Stage Ii ◽  
Research Network ◽  
Stage Iii ◽  
Low Grade ◽  
Bulky Disease ◽  
Purine Analog ◽  
Previously Treated ◽  
Grade Iii

Abstract Introduction: The decision to treat indolent B-cell NHL is often based on progressing bulky disease, worsening symptoms, and increasing hematologic derangement. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies. Combination therapy with pentostatin (P), purine analog, cyclophosphamide (C), alkylator, and rituximab (R), anti-CD20 monoclonal antibody, represents a promising new approach in the treatment of patients with low grade NHL. Most regimens have utilized fludarabine as the purine analog, but the myelosuppression and immunosuppression of these combinations frequently results in severe infections. We have previously reported our experience with pentostatin and rituximab in a cohort of 133 previously treated and untreated patients with Grade III/IV NHL or CLL (2005 Pan-Pacific Lymphoma Conference). Methods: Fifty-five patients have been enrolled in this study with an expected accrual of 100. Patients are being enrolled through the Pharmatech Research Network. Eligibility criteria allows previously treated and treatment naïve patients diagnosed with bulky stage II or low-grade stage III/IV NHL (REAL classification). Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of 8 cycles. Clinical evaluation was performed after even-numbered cycles. Patients were stratified by disease and by prior treatment status. Results: Forty-seven patients have been eligible for evaluation. NHL patients (median age 64, range 30–84) received a total of 236 cycles (median 6). The ECOG status was 0 (65%) and 1 (33%). The overall objective response rate was 70% (CR 21%, Cru 13%, PR 36%). There were 3 grade 4 neutropenias documented and there was a single grade 4 leukopenia. There were a total of 3 deaths all of which occurred within 30 days of the last dose. The first death was due to a second primary, NSCLC, diagnosed after treatment began. The second death occurred in a 81 year-old female (PR) due to CHF and the last death, due to CAD, occurred in an 84 year-old woman (SD). Conclusions: This immunochemotherapeutic regimen is very active in indolent Grade III/IV NHL and the incidence of significant toxities was extremely low. Future trials evaluating the use of R as maintenance therapy following this PCR regimen may also be warranted with an eye toward increasing the overall survival of patients with NHL. The use of combination therapy in elderly patients should be used with caution due to associated co-morbidities.

A Multi-Center, Open-Label Study To Evaluate the Safety and Efficacy of Pentostatin, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated or Treated, Stage III or IV, Low-Grade CLL.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 5045-5045
Author(s):  
Raul R. Mena ◽  
Robert Robles ◽  
David W. Nyman ◽  
Michael Auerbach ◽  
Lalita Pandit
Keyword(s):  
Combination Therapy ◽  
Elderly Patients ◽  
Research Network ◽  
Stage Iii ◽  
Low Grade ◽  
Open Label ◽  
Bulky Disease ◽  
Purine Analog ◽  
Previously Treated ◽  
Grade Iii

Abstract Introduction: The decision to treat indolent CLL is often based on progressing bulky disease, worsening symptoms, and increasing hematologic derangement. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies. Combination therapy with pentostatin (P), purine analog, cyclophosphamide (C), alkylator, and rituximab (R), anti-CD20 monoclonal antibody, represents a promising new approach in the treatment of patients with low grade CLL. Most regimens have utilized fludarabine as the purine analog, but the myelosuppression and immunosuppression of these combinations and the disease of CLL frequently results in severe infections. We have previously reported our experience with pentostatin and rituximab in a cohort of 133 previously treated and untreated patients with Grade III/IV NHL or CLL (2005 Pan-Pacific Lymphoma Conference). Methods: Thirty-five patients have been enrolled in this study through the Pharmatech Research Network (64 sites). The expected accrual is 180 patients. Eligibility criteria allows previously treated and treatment naïve patients diagnosed with low-grade stage III/IV CLL (modified Rai classification). Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of 8 cycles. Clinical evaluation (including CT scan) was performed after even-numbered cycles. Patients were stratified by disease and by prior treatment status. Results: CLL patients (median age 63, range 35–84) have received 138 cycles (median 5.5) so far. ECOG status at enrollment was 0 (80%) and 1 (14%). Overal response rate (N=29 evaluable) was 65% (CR 14%, CRu 7%, PRu 3%, PR 41%). One grade 4 neutropenia has been documented in this cohort. Five deaths have been recorded. One death occurred within 30 days of receiving chemotherapy. This patient (81 YO) was hospitalized 4 days after cycle 1 and death was due to sepsis and multi-organ failure occurred 18 days later. Another death (76 YO) was reported 30 days after cycle 1 due to pneumonia/respiratory insufficinency. An 84 YO patient had treatment delayed after cycle 2, she died at home of an apparent MI. An 83 YO man was hospitalized 2 weeks after completing cycle 2. This patient was dehydrated as a result of gastroenteritis however he developed atrial flutter and died as a result of pulmonary edema. The last patient discontinued therapy after achieving CRu following 3 cycles. Three months later she died of sepsis and pneumonia. Conclusions: This immunochemotherapeutic regimen is active in Grade III/IV CLL and the incidence of significant toxities was low with deaths occurring in elderly patients. Future trials evaluating the use of R as maintenance therapy following this PCR regimen may also be warranted with an eye toward increasing the overall survival of patients with CLL. The use of combination therapy in elderly patients should be used with caution due to associated co-morbidities.

A Multi-Center, Open-Label Study To Evaluate the Safety and Efficacy of Pentostatin, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated or Treated, Stage III or IV, Low-Grade B-Cell Non-Hodgkin’s Lymphoma (NHL) or Bulky Stage II Lymphoma.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 1354-1354
Author(s):  
Raul R. Mena ◽  
Neil P. Christiansen ◽  
Yudhishtra Markan ◽  
Lalita Pandit
Keyword(s):  
Febrile Neutropenia ◽  
B Cell ◽  
Single Agent ◽  
Stage Ii ◽  
Stage Iii ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Purine Analog ◽  
Previously Treated ◽  
Grade 3

Abstract The decision to treat indolent B-cell NHL is often based on progression of the disease. Most regimens have utilized fludarabine as the purine analog but the myelosuppression and immunosuppression of fludarabine combinations frequently results in severe infections. Combination therapy with pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody, based on the single-agent activities, documented synergy, and non-overlapping toxicity profiles, may represent a promising approach in the treatment of these patients. To further investigate the efficacy of the PCR regimen for the treatment of indolent NHL, we conducted a phase II study. Patients diagnosed of bulky stage II, stage III/IV low-grade NHL (REAL classification), previously untreated or treated, were eligible. All patients were treated with intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for at least 8 cycles. 2 additional cycles were given for patients with PR or SD after cycle 8 or patients with CR/CRu first evident at cycle 8. Clinical evaluation was performed after cycles 2, 4, 6, 8, and 10 if necessary. Dose modification for hematologic toxicity may be increased to the previous higher level when a hematologic toxicity returned to normal. Two 25% dose reductions or one 50% dose reduction were allowed for nonhematologic toxicity. One hundred patients with indolent NHL, 68 previously untreated, 26 previously treated, and 6 with unknown treatment history, were enrolled in the study. The median age was 61 years (range 29–84) and 63.4% were ECOG PS 0, 36.6% PS1. A total of 550 cycles were given, with a median of 6 cycles per patient. 8 patients were not evaluated for response due to withdrawal of consent (n=1), unacceptable toxicities (n=3), and missing data (n=4). 92 patients received at least two cycles of treatment and were evaluated for response. The highest response rate (RR) achieved was 68%, with 10 (10%) CR, 12 (12%) CRu, 46 (46%) PR, 23 (23%) SD, and 1 (1%) disease progression. Stratified according to previous treatment status, patients with previously untreated NHL had an RR of 47% (CR, CRu 17%) while that of the previously treated was 17% (CR 7%). 14 (14.0%) patients discontinued treatment due to toxicities. Grade 3/ 4 hematological adverse events documented included 10 grade 4 and 16 grade 3 neutropenia. Infectious complications were noted in 8 patients including 3 grade 3 febrile neutropenia, 2 grade 4 febrile neutropenia, and 3 grade 3 infections. A total of 4 deaths were recorded, including 1 due to acute myocardial infarction, 1 suspected cardiac event and 2 unknown causes. This immunochemotherapeutic regimen is active in patients with indolent NHL. The study is currently on-going and updated results will be presented.

A Multi-Center, Open-Label Study To Evaluate the Safety and Efficacy of Pentostatin, Cytoxan, and Rituxan (PCR) in the Treatment of Previously Untreated or Treated, Bulky Stage II, Stage III or IV, Low-Grade B-Cell NHL.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4709-4709
Author(s):  
Raul R. Mena ◽  
Neal P. Christiansen ◽  
Yudishtra Markan ◽  
Lalita Pandit
Keyword(s):  
B Cell ◽  
Stage Ii ◽  
Stage Iii ◽  
Low Grade ◽  
Open Label ◽  
Eligibility Criteria ◽  
Purine Analog ◽  
Grade 3 ◽  
Intent To Treat ◽  
Anti Cd20

Abstract The decision to treat indolent B-cell NHL is often based on progressive disease, worsening symptoms, and increasing hematological derangement. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies utilizing pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody. P+C+R represents a promising approach in the treatment of these patients. Most regimens have utilized fludarabine (F) as the purine analog but the myelosuppression and immunosuppression of (F) combinations frequently results in severe infections. Eligibility criteria allow both treated and treatment-naïve patients diagnosed with Bulky Stage II or low-grade stage III/IV NHL (REAL classification) to be enrolled. Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of up to 10 cycles. Clinical evaluation was performed after cycles 2, 4, 6, 8 and 10 (if necessary). The intent-to-treat (ITT) population consisted of 76 NHL patients (median age 65, range 29–84) who received a total of 385 cycles (median 6 per patient). The ECOG status was 0 (64%), 1 (36%) and 2 (0%). The overall response rate (CR+Cru+PR) of the 69 evaluable patients was 72% (CR 11.6%, Cru 11.6%, PR 47.8%, SD 27.5% and PD or RD 1.4%). 12 grade 4 and 23 grade 3 neutropenias were documented. There were a total of 5 deaths due to acute myocardial infarction, NSCLC, a suspected cardiac event and 2 unknown cause of death. This immunochemotherapeutic regimen is active in indolent Grade III/IV NHL and the incidence of significant toxicities was low. Future trials evaluating the use of R as maintenance therapy following this PCR regimen may also be warranted with an eye toward increasing the overall survival of patients with NHL. The results will be updated at the meeting.

A multi-center, open-label study to evaluate the safety and efficacy of pentostatin, cytoxan, and rituxan (PCR) in the treatment of previously untreated or treated, stage III or IV, low-grade B-cell non-Hodgkin lymphoma (NHL) or bulky stage II lymphoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 8071-8071
Author(s):  
N. P. Christiansen ◽  
R. Mena ◽  
Y. Markan ◽  
L. Pandit
Keyword(s):  
B Cell ◽  
Stage Ii ◽  
Stage Iii ◽  
Low Grade ◽  
Open Label ◽  
Eligibility Criteria ◽  
Non Hodgkin Lymphoma ◽  
Purine Analog ◽  
Treatment Naïve ◽  
Anti Cd20

8071 Background: The decision to treat indolent B-cell NHL is often based on progressive disease, worsening symptoms, and increasing hematological variations. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies. Combination therapy with these agents, pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody, represents a promising approach in the treatment of these patients. Most regimens have utilized fludarabine (F) as the purine analog but the myelosuppression and immunosuppression of (F) combinations frequently results in severe infections. Methods: Eligibility criteria allow previously treated and treatment-naïve patients diagnosed with bulky stage II or low-grade stage III/IV NHL (REAL classification) to be enrolled. Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of up to 10 cycles. Clinical evaluation was performed after cycles 2, 4, 6 and 8 and 10 (if necessary). Results: The intent-to-treat (ITT) population consisted of 87 NHL patients (median age 62.5, range 29–84) who received a total of 476 cycles (median 6 per patient). The ECOG status was 0 (62.4%), 1 (37.6%) and 2 (0%). The overall response rate of the 80 evaluable patients was 72.5% (CR 11.3%, Cru 12.5%, PR 48.8%). 14 cases of grade 4 and 17 cases of grade 3 neutropenia were documented. There were a total of 4 deaths due to acute myocardial infarction, NSCLC, a suspected cardiac event and 1 unknown cause of death. Conclusions: This immunochemotherapeutic regimen is active in indolent Grade III/IV NHL and the incidence of significant toxicities was low. Future trials evaluating the use of rituximab as maintenance therapy following this PCR regimen may also be warranted with a future goal towards possibly increasing the overall survival of patients with NHL. The presented results are preliminary and the study is currently on-going. No significant financial relationships to disclose.

A multi-center, open-label study to evaluate the safety and efficacy of pentostatin, cytoxan, and rituxan (PCR) in the treatment of previously untreated or treated, stage III or IV, low-grade B-Cell NHL

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7591-7591
Author(s):  
R. R. Mena ◽  
N. P. Christiansen ◽  
D. W. Nyman ◽  
Y. Markan ◽  
N. M. Chowhan
Keyword(s):  
B Cell ◽  
Objective Response ◽  
Stage Iii ◽  
Second Primary ◽  
Low Grade ◽  
Open Label ◽  
Eligibility Criteria ◽  
Purine Analog ◽  
Treatment Naïve ◽  
Anti Cd20

7591 Background: The decision to treat indolent B-cell NHL is often based on progressive disease, worsening symptoms, and increasing hematological derangement. When treatment is indicated, these lymphoproliferative disorders are very sensitive to combination chemotherapies. Combination therapy with these agents, pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody, represents a promising approach in the treatment of these patients. Most regimens have utilized fludarabine (F) as the purine analog but the myelosuppression and immunosuppression of (F) combinations frequently results in severe infections. Methods: Eligibility criteria allow previously treated and treatment-naïve patients diagnosed with low-grade stage III/IV NHL (REAL classification) to be enrolled. Treatment consisted of intravenous infusions of P (4 mg/m2), C (600 mg/m2), and R (375 mg/m2) on day 1 of a 21-day cycle for a total of 8 cycles. Clinical evaluation was performed after cycles 2, 4, 6 and 8. Patients were stratified by disease and by prior treatment status. Results: The intent-to-treat (ITT) population consisted of 54 NHL patients (median age 65, range 30–86) who received a total of 330 cycles (median 6 per patient). The ECOG status was 0 (31%), 1 (58%) and 2 (12%). The overall objective response rate was 71% (CR 15%, Cru 13%, PR 43%). Eight grade 4 neutropenias were documented along with a single grade 4 leukopenia. There were a total of 3 deaths which occurred within 30 days of the last dose. The first death was due to a second primary, NSCLC, diagnosed after treatment began. The second death occurred in an 81 year-old female, who had achieved PR, and her death was due to CHF. The last death, due to MI/CAD, occurred in an 84 year-old woman with SD. Conclusions: This immunochemotherapeutic regimen is active in indolent Grade III/IV NHL and the incidence of significant toxicities was low. Updated trial results will be presented at the ASCO annual meeting. Future trials evaluating the use of R as maintenance therapy following this PCR regimen may also be warranted with an eye toward increasing the overall survival of patients with NHL. No significant financial relationships to disclose.

Carboplatin and chlorambucil combination chemotherapy as treatment for patients with ovarian cancer

1994 ◽  
Vol 4 (1) ◽  
pp. 66-71
Author(s):  
B. D. Evans ◽  
P. Chapman ◽  
P. Dady ◽  
G. Forgeson ◽  
D. Perez ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Small Volume ◽  
Residual Disease ◽  
Stage Iv ◽  
Complete Response ◽  
Stage Ii ◽  
Stage Iii ◽  
Actuarial Survival ◽  
Moderate Volume ◽  
Grade Iii

Fifty-six patients with ovarian cancer (three stage IC, nine stage II, 33 stage III and II stage IV) were treated with carboplatin 350 mg m−2 i.v. day 1 and chlorambucil orally 0.15 mg kgm−1 days 1–7 inclusive, repeated every 28 days for eight courses. The regimen was well tolerated and was virtually free of nephro- and neurotoxicity. Grade III or IV hematology toxicity occurred in 18 patients but only 31 or 330 courses administered were delayed. Of 40 assessable patients eight achieved a clinical/radiologic complete response and 17 a clinical/radiologic partial response. Actuarial survival at 50 months was 65% for stage II patients, 27% for stage III patients and no stage IV patients survived beyond 20 months. Forty-two per cent of patients with residual disease less 2 cm survived 50 months, compared with 44% of patients with moderate volume (2–5 cm) residual disease and 6% of patients with bulk residual disease. This is an active, well tolerated regimen. However, only patients with small volume residual disease have a significant chance of prolonged survival.

scholarly journals Review: Combination therapy in high-risk stage II or stage III colon cancer: current practice and future prospects

2010 ◽  
Vol 2 (4) ◽  
pp. 261-272 ◽  
Author(s):  
Diogo Assed Bastos ◽  
Suilane Coelho Ribeiro ◽  
Daniela de Freitas ◽  
Paulo M. Hoff
Keyword(s):  
Colon Cancer ◽  
High Risk ◽  
Combination Therapy ◽  
Current Practice ◽  
Stage Ii ◽  
Stage Iii ◽  
Future Prospects ◽  
Stage Iii Colon Cancer

Pentostatin and Cyclophosphamide with or without Rituximab Has Significant Activity in Patients with Previously Treated Chronic Lymphocytic Leukemia and Other Low Grade Lymphoid Neoplasms.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3484-3484 ◽  
Author(s):  
Nicole Lamanna ◽  
Matt Kalaycio ◽  
Peter Maslak ◽  
Joseph Jurcic ◽  
David A. Scheinberg ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
Combination Therapy ◽  
B Cell ◽  
Median Number ◽  
Lymphocytic Leukemia ◽  
Low Grade ◽  
Significant Activity ◽  
Purine Analogs ◽  
Heavily Pretreated ◽  
Pretreated Patients

Abstract Combination therapy with purine analogs, alkylators, and/or monoclonal antibodies represents a promising new approach in the treatment of patients with chronic lymphocytic leukemia (CLL) and other low grade B cell neoplasms. Most regimens have utilized fludarabine as the purine analog, but the severe myelosuppression and immunosuppression of these combinations requires careful attention to dosing and schedule to minimize these complications. Of the purine analogs in CLL, pentostatin appears to be least myelosuppressive. We have previously reported our experience with pentostatin and cyclophosphamide (PC regimen) in a cohort of heavily pretreated patients with CLL (JCO21:1278, 2003). We have since added rituximab to this active combination (PCR regimen) and have treated a second cohort of patients with CLL and other low grade B cell neoplasms. We now report on our cumulative experience of 69 patients (23 received PC and 46 received PCR) treated with pentostatin combination therapy. The PC regimen consisted of pentostatin 4mg/m2 and cyclophosphamide 600mg/m2, given every 3 weeks for a total of 6 treatments. In the 2nd cohort of CLL patients, rituximab 375mg/m2 was added to this regimen starting with cycle 2. Supportive measures in both studies included hydration with each treatment (and monitoring of renal function) and prophylactic administration of filgrastim, sulfamethoxazole/trimethoprim, acyclovir, and antiemetics. In the first cohort of patients treated with the PC regimen, the median number of prior treatments was 3 (range 1–5) with the median age being 64 (32–77). There were responses achieved in 74% of patients with 17% complete responses seen in this heavily pretreated group. Similar (or perhaps slightly better) results were obtained with patients treated with the PCR regimen. For this cohort the median age was 62 (30–80) and the median number of prior regimens was 2 (1–7). Of the 32 patients with CLL 28 are evaluable for response: 79% responded and this includes 29% who achieved a complete response. Ten of the 14 patients with other low grade B cell diseases (SLL 8 patients, Waldenstrom’s macroglobulinemia 2 patients, follicular lymphoma 4 patients) are evaluable for response. The overall response rate for these patients was 50% (all PRs). These regimens were generally well tolerated with grade 3/4 toxicity consisting primarily of myelosuppression and its complications. We conclude that PC and PCR are highly active, well tolerated regimens even in heavily pretreated patients. We plan to conduct a multicenter study of PCR as initial therapy in patients with CLL.

A Predictive Model for Limited Stage Diffuse Large B-Cell Lymphoma (DLBCL): A Retrospective Analysis of 1,252 Cases Performed by the Intergruppo Italiano Linfomi (IIL).

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3261-3261
Author(s):  
Sergio Cortelazzo ◽  
Stefano Luminari ◽  
Monica Bellei ◽  
Maurizio Martelli ◽  
Umberto Vitolo ◽  
...  
Keyword(s):  
B Cell ◽  
Retrospective Analysis ◽  
Prognostic Model ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Stage Ii ◽  
Bulky Disease ◽  
Short Survival ◽  
Limited Stage ◽  
Ecog Ps

Abstract Introduction: few studies have explored the usefulness of a prognostic index specifically devised for patients with localized DLBCL. The IIL has performed a retrospective analysis of a large group of patients with limited stage DLBCL and developed a new prognostic model. Results: 1,252 patients with localized (Ann Arbor stage I-II) aggressive B-cell lymphoma (IWF: G or H, WHO:DLBCL) diagnosed from 1988 to 2002 and without CNS involvement, treated by 4 cooperative groups and 2 single institutions, are the subject of this analysis. Patient’s median age was 57 years (range, 17–91) and M/F ratio was 1.26. Clinical stage was I in 239 (19%), IE in 303 (24%), II in 356 (28%) and IIE in 354 (28%) patients, respectively. Supradiaphragmatic disease was present in 56% of patients, 13% had > 3 nodal sites, 53% had extranodal involvement, and 7% had >1 extranodal site. Bulky disease (≥10 cm) was present in 26% of patients, ECOG-PS >1 in 12% and B symptoms in 14%. Abnormal biochemical data included: elevated LDH (28%), β2-microglobulin (B2M;19%) and ESR (38%) and reduced albumin (< 3.5 g/dL) in 21% of the cases. Patients were treated with anthracyclin-containing regimens ± IF-RT. After a median follow-up of 62 months for alive patients (range 1–183 months), 3 and 5-year OS rates were 73% and 71%, respectively. By univariate analysis the following 11 variables were found to be predictive of a short survival: age ≥65 yrs (P=0,0001), stage II nodal (P=0,0001), number of nodal sites (P<0.0001), poor ECOG-PS (P<0.0001), B symptoms (P=0.0009), bulky disease (P=0.0001), elevated ESR (P=0.0001), LDH (P<0.0001), Radiotherapy (P<0.001), B2M (P=0.007) and reduced serum albumin (<0.0001). By Cox multivariate analysis, age ≥65 years (p<0.001), stage II nodal (P<0.001), high LDH (P<0.001) and bulky disease (P<0.01) were indipendent risk factors (RF) for a short survival. The prognostic model was calculated with the sum of scores assigned to each variable; a score of 2 was assigned to advanced age, high LDH, and Bulky; for Stage a score of 1 was considered for stage Ie-IIe and 2 for stage II nodal. Three groups of patients with a different probability of survival (P<0.000001) were identified. Patients at low (Score 0–1; 387 pts), intermediate (Score 2–3; 484 pts) or high risk (Score 4–8; 381 pts) had a 5 years OS of 87%, 77%, 51% respectively. The predictive performance of the model was internally validated through a non parametric Bootstrap method and through residues’ analysis. Conclusions: This prognostic model, developed and validated on a very large series of patients with localized DLBCL, will allow us to select appropriate therapeutic approaches on the basis of different risk categories.

Outcome of Elderly Patients with Diffuse Large B-Cell Lymphoma Treated with R-CHOP: Subgroup Analysis from the UK NCRI R-CHOP 14 Vs 21 Trial

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1516-1516
Author(s):  
Andrea Kühnl ◽  
David Cunningham ◽  
Nicholas Counsell ◽  
Eliza A Hawkes ◽  
Wendi Qian ◽  
...  
Keyword(s):  
Elderly Patients ◽  
B Cell ◽  
Research Funding ◽  
Cell Lymphoma ◽  
B Cell Lymphoma ◽  
Bulky Disease ◽  
Large B Cell Lymphoma ◽  
The Uk ◽  
Large B Cell ◽  
Grade Iii

Abstract Background: Elderly patients with diffuse large B-cell lymphoma (DLBCL) have an inferior prognosis compared to younger patients. Dose intense administration of cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP14) is superior to 3-weekly CHOP in elderly DLBCL patients (Pfreundschuh, Blood 2004), but this benefit has not been demonstrated with addition of rituximab (Delarue, Lancet Oncol 2013). We have previously shown that R-CHOP14 did not improve outcome compared to standard R-CHOP21 in newly diagnosed DLBCL patients aged 19-88 years across all subgroups (Cunningham, Lancet 2013). Here, we provide a detailed subgroup analysis of elderly patients (over 60 years) from the UK NCRI R-CHOP14 vs 21 randomised phase 3 trial. Methods: Between 2005 and 2008, 1080 patients were randomly assigned to receive 8 cycles R-CHOP21 or 6 cycles R-CHOP14 (+ G-CSF) with two additional rituximab applications. Of these, 604 patients were over 60 years and included in the current analysis (301 in the R-CHOP21 arm, 303 in the R-CHOP14 arm), with a median follow-up of 45 months. Results: Baseline characteristics were well balanced between treatment arms. 36% of patients were over 70 years, 15% had a WHO performance status (PS) of 2, 65% stage III/IV disease, 44% bulky disease and 42% B symptoms. There was a trend towards a higher rate of BCL6 rearrangements (26% vs. 16%; P=0.10) and concurrent MYC - and BCL2 rearrangements (double hit lymphoma as determined by FISH, 8% vs. 2%; P=0.06) in the R-CHOP14 arm compared to the R-CHOP21 arm. 85% (257/303) of patients received 8 cycles of R-CHOP14, whereas only 76% (230/301) completed all 8 cycles R-CHOP21. However, percentage of patients receiving at least 6 cycles of therapy was similar (88% and 89%, respectively). Dose delays of myelosuppressive drugs occurred more frequently in patients receiving R-CHOP21 vs. R-CHOP14 (51% vs. 39%; P=0.03) due to a higher incidence of haematological toxicities likely related to the reduced use of G-CSF. G-CSF was mandatory for patients on R-CHOP14 and was given to 57% of patients on R-CHOP21 as secondary prophylaxis. The frequency of dose reductions was similar in the R-CHOP21 and R-CHOP14 arms (15% vs. 16%; P=0.73). Toxicities of grade III+ were seen in 72% and 60% of patients in the R-CHOP14 and R-CHOP21 arms, respectively. There was evidence of a higher incidence of grade III+ neutropenia (62% vs. 36%) and a lower rate of thrombocytopenia (7% vs. 12%) in the R-CHOP21 arm compared to R-CHOP14. The incidence of fever and infections was similar in both arms. There was no evidence of a difference in response rates between the R-CHOP14 and R-CHOP21 arms [complete response (CR)/unconfirmed CR (CRu) rates: 62% vs. 67%, respectively; overall response rate both 91%]. CR/CRu rates after 4 cycles of therapy were 33% and 39% respectively (P=0.15). There was no difference regarding progression-free survival (PFS) and overall survival (OS) between arms, neither in the total cohort of elderly patients, nor in the subgroup of patients over 70 years [OS (all elderly): hazard ratio (HR) 0.91 (95% CI: 0.67-1.24); P=0.55; PFS (all elderly): HR 0.98 (95% CI: 0.74-1.29); P=0.86]. 3-year PFS was 71% (95% CI: 67-74) in all patients over 60 years and 64% (95% CI: 58-71) in patients over 70 years. 3-year OS was 75% (95% CI: 72-79) and 67% (95% CI: 61-74) in patients over 60 years and over 70 years, respectively. In multivariate analysis including individual factors of the International Prognostic Index (IPI), as well as age as continuous variable, gender, presence of B symptoms, bulky disease, b2-microglobulin higher than 3mg/l and albumin higher than 35 g/l, only age was of independent prognostic significance for OS (P=0.01). Besides the standard IPI and the NCCN-IPI, an elderly IPI (E-IPI; Advani, BJH 2010) and the ABE4 score (Prochazka, PLoS One 2014) have been proposed for better prognostication of elderly DLBCL patients. A detailed comparison of these different prognostic models in our dataset will be presented at the meeting. Conclusion: Outcome and toxicities in DLBCL patients over 60 years treated within the NCRI R-CHOP14 vs 21 trial are comparable to results from other randomised studies investigating R-CHOP14 or R-CHOP21 in elderly DLBCL patients. Our data further support the similar efficacy and tolerability of both R-CHOP variants for first-line treatment of this patient group. Disclosures Cunningham: Amgen: Research Funding; Medimmune: Research Funding; Astra Zeneca: Research Funding; Bayer HealthCare Pharmaceuticals: Research Funding; Merrimack: Research Funding; Merck Serono: Research Funding; Celgene: Research Funding; Sanofi: Research Funding. Pocock:Janssen: Honoraria. Ardeshna:Roche: Honoraria.

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