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

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.

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

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.

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 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.

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 II, III or IV CLL.

Blood ◽  
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.

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.

Non-Myeloablative Allogeneic Hematopoietic Transplantation in Relapsed/Primary Refractory Follicular Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 2309-2309
Author(s):  
Claire Fabre ◽  
Christian Recher ◽  
Anne Huynh ◽  
Françoise Rigal-Huguet ◽  
Michel Abbal ◽  
...  
Keyword(s):  
Residual Disease ◽  
Chronic Gvhd ◽  
Conditioning Regimen ◽  
Disease Free Survival ◽  
Stage Iv ◽  
High Rate ◽  
Low Grade ◽  
Bulky Disease ◽  
Free Survival ◽  
Anti Cd20

Abstract Allogeneic stem cell transplantation (SCT) can induce long-term disease-free survival in refractory follicular lymphomas (FL) but is impaired by high rate of transplant-related mortality (TRM). Reduced conditioning followed by allogeneic SCT is a promising concept in FL, allowing a graft-versus-lymphoma (GVL) effect while reducing the TRM. We piloted a clinical trial using this approach in relapsed/primary refractory low-grade lymphomas. From 1998 to 2003, 31 patients (pts) with an HLA-identical sibling have been enrolled. Main pts characteristics were : age = 49 years (range, 32–61 y); grade : I/II FL = 26; FL with histologic transformation = 5; gender = 16 male and 15 female; ≥ 2 prior therapies before transplantation = 23; primary refractory = 8; stage IV = 22; Bulky disease = 16; mean LDH rate before transplantation = 335 UI/l (range, 205–858); residual disease at transplantation (partial response (PR) + progression) = 20. Previous treatments were as follow : anthracyclins = 26, alkylants = 21, anti-CD20 = 15, purine analogs = 7, autologous SCT = 6, radiotherapy = 5. The conditioning regimen was IV fludarabine 30 mg/m²/day (from day −5 to −2); PO busulfan 2 mg/kg/day (from day −7 to −6); antithymocyte globulin (ATG) 2.5 mg/kg/day (from day −4 to −3). 14/31 (45%) and 17/31 (55%) pts received peripheral blood and bone marrow stem cells respectively with a median number of CD34+ cells of 5 x 106/kg (range, 1.8–11.9). Graft-versus-host-disease (GVHD) prophylaxis consisted in cyclosporine A alone. All patients achieved complete donor (> 95%) chimerism after allogeneic SCT. Median duration of neutropenia (< 0.5 G/L) and thrombocytopenia (< 25 G/L) were 3 days (range, 0–16) and 3 days (range, 0–29) respectively. 8/31 pts (26%) had CMV reactivation but no CMV disease. 3/31 (10%) developed grade II–IV acute GVHD. 10/31 (32%) developed chronic GVHD (5 moderate and 5 extensive). The median follow-up time was 20 months. The TRM was 19% (6/31). Causes of death were aGVHD = 1, auto-immune hepatitis = 1, bacteraemia = 2, pulmonary toxoplasmosis = 1 and Lyell syndrome = 1. Overall response rate was 97% (21 CR + 9 PR) at day 100 and at 1 year (24 CR + 6 PR). The estimated 2-year overall survival (OS), event-free survival (EFS) and relapse-free survival (RFS) rate were 75%, 65% and 85% respectively. 2 relapses occurred. Both were treated by anti-CD20, achieved CR and are still alive. Donor age, Bulky disease and LDH were significant for EFS. Altogether, these data suggest that non-myeloablative SCT can induce a high rate of durable remissions with reduced toxicity in this poor risk population.

Rituximab in Combination With Fludarabine Chemotherapy in Low-Grade or Follicular Lymphoma

2005 ◽  
Vol 23 (4) ◽  
pp. 694-704 ◽  
Author(s):  
M.S. Czuczman ◽  
A. Koryzna ◽  
A. Mohr ◽  
C. Stewart ◽  
K. Donohue ◽  
...  
Keyword(s):  
Follicular Lymphoma ◽  
Response Rate ◽  
Complete Response Rate ◽  
Complete Response ◽  
Infectious Complications ◽  
Hematologic Toxicity ◽  
Low Grade ◽  
Similar Response ◽  
Open Label ◽  
Treatment Naïve

Purpose To evaluate the safety and efficacy of fludarabine plus rituximab in treatment-naïve or relapsed patients with low-grade and/or follicular non-Hodgkin's lymphoma. Patients and Methods This was an open-label, single-arm, single-center phase II study enrolling 40 patients. During the first week of the study, patients received two infusions of rituximab 375 mg/m2 administered 4 days apart. Seventy-two hours after the second infusion of rituximab, patients received the first of six cycles of fludarabine chemotherapy (25 mg/m2/d for 5 days on a 28-day cycle). Single infusions of rituximab were administered 72 hours before the second, fourth, and sixth cycles of fludarabine, and two infusions of rituximab were given 4 weeks after the last cycle of fludarabine. Treatment duration was 26 weeks. Results An overall response rate of 90% (80% complete response rate) was achieved in the intent-to-treat population. Similar response rates were seen in treatment-naïve and previously treated patients. The median duration of response has not been reached at 40+ months. The median follow-up time in this study is 44 months (range, 15 to 66 months). In patients positive for the 14;18 translocation in blood and/or marrow at enrollment, molecular remission was achieved in 88% of cases, with patients remaining negative for up to 4 years to date. Hematologic toxicity was manageable, and except for a 15% incidence of herpes simplex/zoster infections, infectious complications were rare. Nonhematologic toxicities were minimal. Conclusion Rituximab plus fludarabine was well tolerated and associated with an excellent complete response rate, including molecular remissions, in patients with low-grade or follicular lymphoma.

A Combination of Rituximab with Chemotherapy in Low Grade Lymphoma.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4647-4647 ◽  
Author(s):  
Suresh B. Katakkar
Keyword(s):  
Disease Free Survival ◽  
Stage Iv ◽  
Stage Iii ◽  
Low Grade ◽  
Open Label ◽  
Open Label Study ◽  
Mortality And Morbidity ◽  
Complement Dependent Cytotoxicity ◽  
Disease Free

Abstract Introduction: The combination of rituximab with conventional chemotherapy is superior to rituximab therapy alone. Maintanence of chemo-immunotherapy, done for two years at a fixed interval based on pharmacokinetics of Rituximab, may give long term remission improving disease free intervals. Rationale: MoAb therapy works not only by recruitment of FcR but also by complement dependent cytotoxicity(CDC) and growth arrest and/or apoptosis. Methodology: This was an open label study. Pts with follicular and diffuse small cleaved-cell NHL stage III and IV were eligible. Induction chemotherapy consists of Cytoxan 650 mg/m2 iv, Vincristine 1mg/m2, Prednisone 50mg/m2 po for 7 days, repeated Q3 weeks. Rituximab was given 375mg/m2 iv Q week for 6 weeks. After 10 weeks of completion of Rituximab, pts were maintained on Rituximab 375 mg/m2 iv Q week for 6 weeks with only one chemotherapy in week 3. CT/PET scan done Q 3 months. Results: 42 patients; 20 females and 22 males, median age 58. 18 stage III and 24 stage IV. 91%(38/42) went into CR with induction and 1st maintanence therapy. Remaining 4 went into remission after all 6 sessions. Only 3 have relapsed of which 1 is in CR again with reinduction. Thus 39/42 are in CR for a median of 47 months. The toxicity was minimal, with 5% fever chills and hypotension. All responded well to premedication with tagamet and corticosteroid; given iv. 2% incidence of neutropenia. Two patients had sepsis. Conclusions: 1. The induction and maintanence with Rituximab with addition of chemotherapy is synergistic. 2. It has prolonged the disease free survival. 3. Time to disease progression is prolonged and the final duration of remission is not reached. 4. The toxicity is acceptable, though the treatment is expensive. 5. This chemo-immunotherapy may eliminate microscopic disease and avoid stemcell transplant and associated mortality and morbidity.

The Revised International Prognostic Index (R-IPI) Score Is Predictive Of Survival In Aggressive Transformed Lymphomas (TL) From Low Grade Non-Hodgkin Lymphomas In The Chemoimmunotherapy Era

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4275-4275 ◽  
Author(s):  
Tsao Christina ◽  
Samir Dalia ◽  
Celeste M. Bello ◽  
Lubomir Sokol ◽  
Eduardo M. Sotomayor ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
International Prognostic Index ◽  
Prognostic Index ◽  
B Cell Lymphoma ◽  
Stage Iii ◽  
Low Grade ◽  
Cell Transplant ◽  
Bulky Disease ◽  
Histological Transformation ◽  
Extranodal Disease

Abstract Introduction Histologic transformation of low grade non Hodgkin lymphoma (LG-NHL) occurs with a variable frequency. Several factors have been associated with survival in transformed lymphoma (TL) and the prognosis has been generally poor. The R-IPI has been shown to be prognostic in the pre rituximab era. Purpose To assess R-IPI as prognostic at lymphoma transformation in the rituximab era. Methods Patients with a diagnosis of diffuse large B-cell lymphoma transformed from LG-NHL (DLBCL-TL) were identified between January 2001 and December 2011 through the Moffitt Cancer Center Total Cancer Care Database. LG-NHL included follicular lymphoma (FL), marginal zone lymphoma (MZL), mucosa associated tissue lymphoma (MALT) and other low grade histologies. Patients with small lymphocytic lymphoma (SLL) with Richter’s transformation were excluded. All patients received rituximab based chemotherapy at transformation. Clinical data, pathologic data include morphology and immunohistochemistry (IHC) including CD10, BCL6, MUM1/IRF4 were recorded. Overall survival (OS) was calculated from the date of transformation. OS was estimated by the Kaplan-Meier method and compared using the long-rank test. A p-value< 0.05 was considered statistically significant. Results A total of 81 patients were identified with DLBCL-TL. At diagnosis and transformation the median ages were 60 and 64 years (22 – 89), respectively. The male:female ratio was 0.72. The most common LG-NHL diagnosis was FL (75.3%). The median time to DLBCL transformation (TTT) was 3.4 years. At LG-NHL diagnosis 67.9% of patients were stage III/IV, 23.5% had bulky disease, 35.8% had extranodal disease (ED) and 14.8% were FLIPI1 score > 3. At transformation 29.6% had B symptoms, 77.8% had stage III/IV disease, 25.9% had ED, and 40.4% had an elevated LDH. DLBCL-GCB as per Hans algorithm was present in 65.5% of cases at transformation. The mean hemoglobin (Hb) and serum albumin (SA) level at transformation were 12.6 g/dl and 3.9 g/dl, respectively and an IPI > 3 was present in 22.2% of cases. R-IPI categories were very good in 4.9%, good in 72.8% and poor in 22.2%. Patients received rituximab prior to transformation in 65.4% with R-CHOP being the most common regimen used (84%). Radioimmunotherapy (RIT) was given in 17.3% of patients. Patients received 3 or more treatment lines in 74.1%. Patients underwent autologous and allogeneic stem cell transplant in 24.7 and 2.5% of cases, respectively. The median OS was 6.2 years. Poorer OS was associated with R-IPI > 3 at transformation (median OS 1.9 y, HR 2.9 [CI 1.5 – 5.9], p<0.0001) (Figure 1), FLIPI1 score 3 or more (median OS 1.7y, HR 2.9 [CI 1.7 – 5.1], p<0.0001), TTT< 2 years (median OS 2.8y, HR 3.2 [0.9 – 10.5], p=0.041), B symptoms (median OS 2.8y, HR 3.1 [1.5 – 6.4] p=0.003) and elevated LDH (median OS 2.8y, HR 2.6[1 – 6.6], p=0.04). The median OS with IPI< 2 was not reached. No survival differences were seen with FL vs non FL histology, older age, extranodal disease, bulky disease, use of RIT, number of treatment lines or rituximab prior to TL. There was a trend towards poorer OS with SA< 3.7 g/dl (median OS 2.8y, p=0.068). Conclusions An R-IPI >3 at transformation was associated with poorer OS in patients with LG-HNL who undergo histological transformation into DLBCL and treated with chemoimmunotherapy. This suggests that R-IPI can be used at the time of transformation to better assess the aggressiveness of disease. A confirmation of these findings will be needed in multicenter and prospective cohorts. Disclosures: No relevant conflicts of interest to declare.

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