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

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.

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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 ◽

10.1182/blood.v108.11.4709.4709 ◽

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.

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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

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.7591 ◽

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.

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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

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.6606 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 6606-6606

Author(s):

D. W. Nyman ◽

R. Mena ◽

R. Robles ◽

M. Auerbach ◽

L. Pandit

Keyword(s):

Stage Iii ◽

Low Grade ◽

Open Label ◽

Eligibility Criteria ◽

Bulky Disease ◽

Treatment Naïve ◽

Acute Mi ◽

Asco Meeting ◽

Intent To Treat ◽

Anti Cd20

6606 Background: The decision to treat indolent CLL is often based on progressive bulky disease, worsening symptoms, and increasing hematological derangement. When treatment is indicated, these lymphoproliferative disorders are sensitive to combination immunochemotherapies utilizing pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), a potent anti-CD20 monoclonal antibody. P+C+R represents a promising new approach in the treatment of patients with low grade CLL. Methods: Eligibility criteria allow 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 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 41 CLL patients (median age 64, range 36–85) who received a total of 207 cycles (median 4 per patient). ECOG status at enrollment was 0 (66%), 1 (27%) and 2 (7%). The overall response rate was 61% (CR 13%, PR 48%). One grade 4 neutropenia was documented. Four deaths have been recorded. An 81 YO patient was hospitalized 8 days after cycle 1; death, due to sepsis, occurred 22 days later. The death of an 83 YO was reported 10 days after cycle 2 as a result of an acute MI. An 83 YO patient, who developed gastroenteritis, was hospitalized 10 days after cycle 2. This progressed to dehydration and atrial flutter. Death came as a result of pulmonary edema and ASHD. An 82 YO man was hospitalized 4 days after completing cycle 2. He presented with extreme dyspnea but cause of death was CLL. Conclusions: This immunochemotherapeutic regimen is active in Grade III/IV CLL and the incidence of significant toxicities was low with deaths occurring only in elderly (>80 YO) patients. Updated results of this trial will be presented at the ASCO meeting. No significant financial relationships to disclose.

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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 ◽

10.1182/blood.v110.11.1354.1354 ◽

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.

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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

Journal of Clinical Oncology ◽

10.1200/jco.2007.25.18_suppl.17508 ◽

2007 ◽

Vol 25 (18_suppl) ◽

pp. 17508-17508

Author(s):

R. R. Mena ◽

R. Robles ◽

M. Auerbach ◽

M. Moezi ◽

D. Headley

Keyword(s):

Low Grade ◽

Open Label ◽

Eligibility Criteria ◽

Bulky Disease ◽

Clinical Evaluations ◽

Treatment Naïve ◽

Grade Ii ◽

Previously Treated ◽

Intent To Treat ◽

Anti Cd20

17508 Background: The decision to treat indolent CLL is often based on progressive bulky disease, worsening symptoms, and increasing hematological variations. When treatment is indicated, these lymphoproliferative disorders are sensitive to combination immunochemotherapies utilizing pentostatin (P), a purine analog, cyclophosphamide (C), a DNA alkylator, and rituximab (R), an anti-CD20 monoclonal antibody. PCR represents a promising new approach in the treatment of patients with low grade CLL. Methods: Eligibility criteria allow previously treated and treatment-naïve patients diagnosed with low-grade stage II/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 up to 10 cycles. Clinical evaluations (including CT scan) were performed after cycles 2, 4, 6, 8, and 10 (if necessary). Results: The intent-to-treat (ITT) population consisted of 80 CLL patients (median age 64, range 35–83) who received a total of 368 cycles (median 5 per patient). ECOG status at enrollment was 0 (68.4%), 1 (27.6%) and 2 (3.9%). The overall response rate of the 59 evaluable patients was 61% (CR 6.8%, Cru 16.9%, PR 37.3%). 7 cases of grade 4 neutropenia, 2 cases of grade 4 respiratory distress, and 1 case of grade 4 anemia were reported. 5 deaths, all in elderly patients (>70 years old), have been recorded, due to acute respiratory failure, myocardial infarction, pulmonary edema, sepsis, and one unknown cause of death. Conclusions: This immunochemotherapeutic regimen is active in Grade II/III/IV CLL and the incidence of significant toxicities was low with deaths occurring only in elderly (>80 YO) patients. The presented results are preliminary and this study is currently on-going. No significant financial relationships to disclose.

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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 ◽

10.1182/blood.v106.11.4750.4750 ◽

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.

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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 II, III or IV CLL.

Blood ◽

10.1182/blood.v108.11.4978.4978 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4978-4978

Author(s):

Raul R. Mena ◽

Robert Robles ◽

Michael Auerbach ◽

Mehdi M. Moezi ◽

David Headley

Keyword(s):

Stage Ii ◽

Open Label ◽

Eligibility Criteria ◽

Bulky Disease ◽

Old Patients ◽

Open Label Study ◽

New Approach ◽

Study Results ◽

Intent To Treat ◽

Anti Cd20

Abstract The decision to treat indolent CLL is often based on progressive bulky disease, worsening symptoms, and increasing hematological derangement. When treatment is indicated, these lymphoproliferative disorders are sensitive to combination immunochemotherapies 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 new approach in the treatment of patients with CLL. Eligibility criteria allow both treated and treatment-naïve patients diagnosed with Stage II/III/IV CLL (modified Rai 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 (including CT scan) was performed after cycles 2, 4, 6, 8 and 10 (if necessary). The intent-to-treat (ITT) population consisted of 70 CLL patients (median age 64, range 35–83) who received a total of 286 cycles (median 4.5 per patient). ECOG status at enrollment was 0 (68%), 1 (28%) and 2 (4%). The overall response rate (CR+Cru+PR) of the 50 evaluable patients was 52% (CR 8%, Cru 14%, PR 30%, SD 46% and PD or RD 2%). 2 grade 4 neutropenia and 1 grade 4 respiratory distress was documented. 4 deaths have been recorded, all in elderly patients (>80 years old), due to acute respiratory failure, myocardial infarction, pulmonary edema and sepsis. This immunochemotherapeutic regimen is active in Stage II/III/IV CLL and the incidence of significant toxicities was low with deaths occurring only in elderly (>80 years old) patients. The study results will be updated at the meeting.

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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 ◽

10.1182/blood.v106.11.5045.5045 ◽

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.

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LR-CD: Lenalidomide combination therapy for untreated low-grade B-cell NHL.

Journal of Clinical Oncology ◽

10.1200/jco.2012.30.15_suppl.8053 ◽

2012 ◽

Vol 30 (15_suppl) ◽

pp. 8053-8053

Author(s):

Craig B. Reeder ◽

Rodger Edwin Tiedemann ◽

Katherine Gano ◽

Amylou C. Dueck ◽

Christoher R Conley ◽

...

Keyword(s):

B Cell ◽

Single Agent ◽

B Cell Lymphoma ◽

Median Number ◽

Low Grade ◽

Response Data ◽

Non Hodgkin Lymphoma ◽

Best Response ◽

Treatment Naïve ◽

Reported Data

8053 Background: Lenalidomide (LEN) is an immunomodulatory agent that has shown significant single-agent anti-lymphoma activity in patients with relapsed disease and in combination may enhance the efficacy of rituximab by various mechanisms. There is limited data on the role of LEN in combination regimens for treatment-naïve patients. This phase II single arm trial was designed to evaluate tumor response, toxicity (AE) and survival with a combination of LEN, rituximab, cyclophosphamide (CTX) and dexamethasone (DEX) (LR-CD) in symptomatic untreated patients with low grade B-cell non-Hodgkin lymphoma. Methods: Eligibility required age ≥18, ECOG PS ≤2, confirmed diagnosis of low-grade B-cell lymphoma (FL1-2, SLL, MZL or LPL/WM), measurable nodes ≥2cm or IgM ≥400mg/dL(LPL/WM), ANC ≥1400/mm3, platelets ≥100,000/mm3, creatinine ≤2mg/dL, signed informed consent and in need of therapy. Treatment consisted of IV rituximab 375mg/m2 D1, oral LEN 20mg D1-21, CTX 250mg/m2 D1, 8, 15, DEX 40mg D1, 8, 15, 22 and ASA 325 mg daily in a 28 day cycle. Treatment continued 2 cycles beyond best response (max 12). Toxicity was assessed by NCI CTCAE v3.0. Results: 28 patients have enrolled at Mayo Clinic with 25 evaluable for toxicity and 21 for response: Median age 65(43-83), 72% male, FL 24%, MZL 28%, LPL/WM 38%, and SLL 4%. Median number of cycles given was 5. Overall response in 21 patients with response data is 95% (95% CI 76-100%) with 19% CR (95% CI 5-42%), and 76% PR (confirmed and unconfirmed, 95% CI 53-92%). The ORR in 8 patients with LPL/WM with response data was 88%, all PR (95% CI 47-100%). At a median f/u of 14.7 months 96% are alive without progression. 1 death (unrelated) occurred 7.7 months after completing 12 cycles of treatment. The most common grade ≥3 AEs were neutropenia (37.5%), leukopenia (16.7%), anemia (12.5%) and fatigue (12.5%). Conclusions: The combination LR-CD with the novel agent LEN is feasible, well tolerated and produces high response rates in symptomatic patients with low grade B-cell NHL. Toxicities are manageable and similar to reported data of single agent LEN.

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