Impact Of a Federal Program On  response Rate & Survival, In a Cohort Of Patients With Diffuse Large B- Cell Lymphoma. Analysis In a Single National Reference Institution In Mexico

Abstract The actual standard of care of Diffuse Large B-Cell Lymphoma (DLBCL) includes rituximab in combination with chemotherapy, with overall response rates up to 76 %. However, this treatment may not be accessible to many patients because of limited economical resources, particularly in developing countries, where most of the treatment must be paid from the pocket of patients or their families. In Mexico, since 2011 a Federal program has fully covered the treatment of patients with DLBCL. At the Instituto Nacional de Cancerología (INCan) in Mexico city 214 patients with ths disease have been treated without cots with the standard of care. The mean age at diagnosis was 56.7 +15.9 (22-91). This series of cases was compared with a retrospective analysis of cases with DLBCL seen at the INCan between 2006-2008 None A total of 264 cases were retrospectively analyzed. No differences were found in demographic and clinical characteristics at the time of diagnosis. However, a clear positive impact was found in the group that received full treatment thanks to this new social coverage by this new social security program. The follow-up and completion of treatment was 99%., In contrast: from 264 in the retrospective group, 209 (79 %) were treated, but only 29 (10.9 %) were able to receive an optimal treatment, including rituximab. These differences in treatments had a clearly impact on the response rate, as shown in the following table:A: Retrospective cases.N (%) B: Cohort.N (%) p Patients. 264 214 -- Treatment:CHOP-R (standard of care)CHOP0-2 cycles** 2918055** 20410*-- 0.001 Response (all patients) :CompletePartialStable diseaseProgressiveNot evaluable, lost of follow up 103 (39)31 (11.7)11 (4.1 )24 (9)95 (36) 124 (58)19 (8.8)0 --29 (13.5)-- 0.001 Relapse rate (%) 93 (35 %) 43 (20%) 0.0001 *7 patients did not received rituximab because of HBV & 3 HIV positive had < 100 absolute CD4 counts.**Patients who abandoned treatment because of reduced economical resources. These results demonstrate the importance of social programs that may accessible standard treatment options in countries with limited resources. Disclosures: No relevant conflicts of interest to declare.

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Favorable Results of Rituximab in Combination with CHOP in the Front-Line Treatment of Follicular Lymphoma Grade 3.

Blood ◽

10.1182/blood.v108.11.2770.2770 ◽

2006 ◽

Vol 108 (11) ◽

pp. 2770-2770

Author(s):

Luis Fayad ◽

Michael Overman ◽

Barbara Pro ◽

Peter McLaughlin ◽

Felipe Samaniego ◽

...

Keyword(s):

Follicular Lymphoma ◽

B Cell ◽

Response Rate ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Bulky Disease ◽

Large B Cell Lymphoma ◽

Grade 3 ◽

Large B Cell

Background: Follicular lymphoma grade 3 has a natural history that is more akin to that of diffuse large B-cell lymphoma. The addition of rituximab to standard CHOP has resulted in improved response and survival in diffuse large B-cell lymphoma. Information about outcomes in follicular lymphoma grade 3 is lacking. Methods: A single institution retrospective review of patients with follicular grade 3 lymphoma evaluated at the UTMDACC from 1999 to 2004. Patients were located from the UTMDACC lymphoma database. All patients were initially treated with R-CHOP. Results: Forty-five patients were identified: 51% male, 47% ≥60 years, and 87% follicular grade 3b. The LDH was elevated in 24%, ECOG performance status was >1 in 2%, and >1 site of extranodal involvement was present in 10%. Stage distribution was 11% stage I, 11% stage II, 42% stage III, and 36% stage IV, bulky disease (>7cm) was present in 11%, and B symptoms occurred in 13%. Beta-2 microglobulin was elevated in 57% with values >3 μg/dL in over 50%. IPI distribution was: 46% IPI Low, 38% LI, 11% IH, and 4% IPI High. Overall response rate was 100% with 96% complete responses. Relapse rate by IPI category was 24% for Low IPI, 18% for IPI LI, and 40% for IPI IH, and 100% for the two patients with High IPI. With median follow-up of 33 months, three year failure-free survival (FFS) is 73% (95% CI: 59 to 87%). One patient died (2%) with an overall survival (OS) at three years of 97% (95% CI: 93 to 100%). Conclusion: The addition of rituximab to CHOP provided a high response rate and excellent early survival in this group of mostly good prognosis patients. Relapses were still seen; longer follow-up is needed.

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Concurrent Follicular Lymphoma At Diagnosis Has a Negative Impact On The Outcome Of Patients With Diffuse Large B Cell Lymphoma

Blood ◽

10.1182/blood.v122.21.4260.4260 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4260-4260 ◽

Cited By ~ 2

Author(s):

David Wrench ◽

Hasan Rizvi ◽

Andrew Wilson ◽

Ciaran O'Riain ◽

Andrew Clear ◽

...

Keyword(s):

Follicular Lymphoma ◽

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

Negative Impact ◽

Tissue Sample ◽

B Cell Lymphoma ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract In contrast to either de novo diffuse large B cell lymphoma (dnDLBCL) or follicular lymphoma (FL) that transforms to DLBCL, the clinical course of DLBCL and FL presenting simultaneously (DLBCL/FL) is not well characterised. From 1 October 1975 to 31 December 2010, 819 patients were diagnosed with DLBCL at St Bartholomew’s Hospital. Twenty-seven patients with bone marrow (BM) involvement were excluded because of histologies other than FL or DLBCL in the BM (n=2) or unavailable BM samples (n=25). The remaining patients comprised the study population (n=792) which consisted of 45 histologically confirmed DLBCL/FL and 747 dnDLBCL. A pathological review was performed of all DLBCL/FL and all the positive BM samples. Remission duration (RD), progression-free survival (PFS), overall survival (OS) and lymphoma-specific survival (LSS) were compared in DLBCL/FL and dnDLBCL. DLBCL/FL comprised composite (both histologies in the same tissue sample; n=24) and discordant (both histologies in separate tissue samples; n=21) lymphoma. The majority (n=18, 75%) of composite DLBCL/FL were diagnosed on lymph node (LN) sampling with the remainder identified in tonsil (n=3) with single cases in testis, salivary gland and BM. Discordant DLBCL/FL, presented as DLBCL and FL involving LN and BM respectively in 16 cases (76%). Other combinations included DLBCL and FL in separate LNs (n=2) and one each of kidney + BM, mesentery + LN, bone biopsy + BM. At presentation, DLBCL/FL had more advanced stage (p<0.01), higher IPI (p=0.02) and lower Hb (p=0.02) than dnDLBCL in keeping with BM involvement rates of 19/45 (42%) and 32/747 (4%), respectively. Most DLBCL/FL (n=42; 93%) received anthracycline based combination chemotherapy (a single case received HD-MTX and 2 cases palliative / no treatment both of whom died within 3.5 months) and, since 2003, addition of rituximab (24% of cases) to CHOP (n=10) or CODOX-M/IVAC (n=1); with similar rates of anthracycline (82%) and rituximab (29%) use in dnDLBCL. The 44 documented responses in DLCBL/FL included complete response (CR, n=26; 59% similar to 66% in 696 patients with dnDLBCL and assessable responses), partial response (n=7) and stable disease/progression (n=11) with a shorter RD for DLBCL/FL (median 8.7 yrs) compared to dnDLBCL (median not reached), although this was not statistically different (p=0.09). PFS was significantly shorter for DLBCL/FL in comparison with dnDLBCL (2.0 versus 4.6 yrs, respectively; p=0.02) and DLBCL/FL not achieving CR had inferior OS (0.4 yrs) than those achieving CR (11.5 yrs; p<0.01). Relapse after CR occurred in 12/26 (46%) patients with DLBCL/FL and in 142/456 (31%; p=0.13) of those with dnDLBCL; 83% and 87% relapsed cases have died, respectively. With a median follow-up of 10 yrs, 71% patients with DLBCL/FL have died as compared to 65% patients with dnDLBCL, and no differences in median OS were observed (4.0 yrs for DLCBL/FL versus 5.5 yrs for dnDLBCL; p=0.28). Death was most commonly due to lymphoma, the rate being similar in patients with DLBCL/FL (56%) and dnDLBCL (52%). However, LSS was shorter for DLBCL/FL (6.3 yrs) than dnDLBCL (13.8 yrs; p<0.01) and, with the long follow-up, we found no differences in OS between DLBCL with concordant (DLBCL, n=32) or discordant (FL, n=18) BM involvement (p=0.38). This study, to the authors’ knowledge the largest series of concurrent FL and DLBCL, confirms the relative frequency of DLBCL/FL to DLBCL (45:747, 6%) and demonstrates that the simultaneous presence of FL negatively influences the outcome of patients with DLBCL, by shortening PFS and LSS. This data emphasizes the importance of thorough staging at diagnosis, including BM biopsies, and highlights the need for better management of this population, which has a worse prognosis than dnDLBCL and is frequently excluded from clinical trials. Disclosures: No relevant conflicts of interest to declare.

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Clinical Pharmacokinetic (PK) and Safety (Immunogenicity) of Rituximab Biosimilar RTXM83 in Combination with Chemotherapy CHOP in Patients with Diffuse Large B-Cell Lymphoma (DLBCL)

Blood ◽

10.1182/blood.v124.21.5472.5472 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5472-5472 ◽

Cited By ~ 5

Author(s):

Amalia Florez ◽

Thiago Di Matteo ◽

Gloria Fresnillo ◽

Consuelo Tudela ◽

Mauricio Seigelchifer ◽

...

Keyword(s):

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

Analytical Data ◽

B Cell Lymphoma ◽

Assay Sensitivity ◽

Large B Cell Lymphoma ◽

Large B Cell ◽

The Eu

Abstract Background: RTXM83 is a rituximab biosimilar candidate manufactured by MAbxience Company. Full spectrum of physicochemical and preclinical studies showed biosimilarity of RTXM83 and originator drug MabThera®/Rituxan® marketed by Roche. MabThera®/Rituxan® product is approved to treat Non-Hodgkin´s Lymphoma, chronic lymphocytic leukemia and rheumatoid arthritis in the EU and US, plus it is approved to treat Diffuse Large B-cell lymphoma (DLBCL) in the EU. Rituximab is also used for other types of lymphoma (e.g. Mantle cell lymphoma) in certain parts of the word. Objective: To demonstrate comparable pharmacokinetics (PK) and safety profile (immunogenicity) to MabThera®, a clinical PK/immunogenicity analysis was designed to compare RTXM83 and MabThera® when administered with CHOP to patients with DLBCL. Methods: Analysis of an interim PK/Safety report from randomized and blinded study, where 24 patients with newly diagnosed DLBCL treated with R-CHOP as part of a multi-center study undertaken to assess the PK and immunogenicity. R-CHOP (rituximab-375mg/m2; cyclophopsphamide-750mg/m2; adriamycin-50mg/m2; vincristine-1.4mg/m2 on day 1 and prednisolone-60mg/m2 on days 1 to 5) was given every 3 weeks for a total of 6 cycles. The PK analysis were conducted on quality control (QC) checked analytical data for Cycle 1 and Cycle 6 using nominal blood sampling times. PK parameters were determined from the serum Rituximab concentration-time profiles obtained following administration of the first (Cycle 1) and last intravenous infusion of study medication (Cycle 6) using non-compartmental procedures in Phoenix WinNonlin (Version 6.2.1). The immunogenicity assessments were based on a specific and validated method for systematic evaluation of an unwanted immune response against RTXM83 and MabThera®. In fact, a confirmatory assay and specific cut point was established as current described recommendations in white papers and guidance documents. This part assures the assay sensitivity and a “characterization step” in the study sample analysis. A screening assay that picks up 5% positives that are subsequently shown to be due to non-specific binding in a confirmatory (immunodepletion) assay provides assurance that true low positives can be detected. Finally, the clinical immunogenicity measurements were performed on Cycle 5, Cycle 6 and follow-up patient samples. Results: Following the end of infusion of 375 mg/m2 q3w RTXM83 or MabThera® (Rituximab) (3 hours infusion) administered in combination with CHOP in Cycle 1 and Cycle 6, serum concentrations of Rituximab declined steadily in a generally bi-phasic manner. The arithmetic mean ±SD of PK parameters (T1/2(hrs); Cmax (ug/ml); Cmin (ug/ml); AUC0-∞ (ug*hrs/ml) of Rituximab during cycle 1, cycle 6 and follow-up patients were determined. All these data are comparable with values previously reported for rituximab in other conditions. No anti-drug antibody case was reported, so RTXM83 and MabThera® displaying null or undetectable immunogenicity. Conclusions: The data indicate that therapeutic levels of rituximab (RTXM83/Mabthera®) were observed across studied cycles. All data are comparable with values previously reported for rituximab. Therefore, PK profile and immunogenicity profile of RTXM83 is comparable with Mabthera® in treating DLBCL. Disclosures No relevant conflicts of interest to declare.

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Doublet Versus Triplet PET: Is END of Therapy PET Needed IF Interim PET Is Negative in Hodgkin'S or Diffuse Large B CELL Lymphoma?

Blood ◽

10.1182/blood.v128.22.5354.5354 ◽

2016 ◽

Vol 128 (22) ◽

pp. 5354-5354

Author(s):

Imran K Tailor ◽

Bilal Btoosh ◽

Shaimaa Hamdy ◽

Shanker Raja ◽

Mohammed O Alharbi ◽

...

Keyword(s):

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

Progression Free Survival ◽

B Cell Lymphoma ◽

Standard Of Care ◽

Complete Response ◽

Interim Pet ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Introduction: Baseline (PETb) and end of therapy (PETe) FDG PET is standard of care in the management of hodgkin's lymphoma (HL) and diffuse large B cell lymphoma (DLBCL). The role of interim PET (PETi) in HL is well established while its role in DLBCL is not well defined. We evaluated the utility of triPET (PETb, PETi and PETe ) in management of these two lymphomas. Methods: Retrospective review of PET archives revealed a total of 37 pts (HL=22, DLBCL=15). TriPET were acquired per accepted protocol. SUVmax and Deauville scores (DSc) were obtained from five target lesions, the average i.e. composite SUVmax & DSc were computed for each pt. Statistical analyses were performed with the composite maxSUV (cSUV) and Deauville scores (cDSc) (using EXCEL). Following statistics were performed (separately and combined in HL and DLBCL); mean+SD, PPV and NPV for complete response (CR) Vs. progressive disease (PD) on PETi using the following variables 1. cSUV and 2. cDSc and 3. delta change (DELT). Median progression free survival (PFS) was the clinical endpoint for response. Results: The mean PFS in our group was 17 and 15 months in HL and DLBCL respectively. Using cut off thresholds for intP to predict CR at cSUV<=2.0, , cDSC<=2.0 and DELT >=80%,. In HL: for cSUV- PPV 67%, NPV 95%; for DELT of cSUV PPV 100%, NPV 95%; for cDSC-PPV 30%, NPV 100%. In DLBCL: for cSUV- PPV 25%, NPV 100%; for DELT of cSUV PPV 33%, NPV 100%; for cDSC- PPV 50%, NPV 100%. Conclusion: The results from our series suggest that PETi has a role not only in HL but in DLBCL as well. Our modest cohort suggests that a negative PETi in DLBCL had a NPV of 100% across cSUV, cDSc and DELT, with regards to CR. Our data also suggests that PETe is not needed if PETi is -ve. While in HL subset, our results concur with results from other groups, this needs to be validated in a larger series. Disclosures No relevant conflicts of interest to declare.

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Primary mediastinal large B-cell lymphoma: Treatment outcomes in 43 patients

Journal of Clinical Oncology ◽

10.1200/jco.2006.24.18_suppl.17556 ◽

2006 ◽

Vol 24 (18_suppl) ◽

pp. 17556-17556

Author(s):

C. L. Mello ◽

O. Feher ◽

V. C. Lima ◽

C. Valadares ◽

F. A. Soares ◽

...

Keyword(s):

B Cell ◽

First Generation ◽

Response Rate ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Third Generation ◽

First Line ◽

Large B Cell Lymphoma ◽

Large B Cell

17556 Objectives: Primary mediastinal B-cell Lymphoma (PMBL) is recognized as a separate entity in the WHO classification. Treatment for PMBL is based on a combination of conventional dose chemotherapy, high dose chemotherapy and radiation therapy. The best strategy is still undefined. We conducted a retrospective analysis of patients with PBML to identify clinical prognostic factors. Methods: A retrospective analysis of 43 patients treated at Hospital do Cancer AC Camargo, Sao Paulo, Brazil, between 1989 and 2004. All patients had previous diagnosis of diffuse large B-cell lymphoma, with positive CD20 on neoplastic cells. A predominant anterior mediastinal lesion should be present. Induction chemotherapy regimens were grouped in first generation (CHOP/CHOP-like), third generation (PromaceCytabon/MACOP) and other (pediatric regimens, COP). Results: Age ranged from 16 to 82 years-old, 30 females and 13 male. Age < 35 yo was associated with a better prognosis (5 years OS - 56% × 34%, p = 0.048). Among clinical variables, female gender, stage IA-IIB, IPI 0–1, normal LDH, absence of mediastinal bulky disease were associated with better prognosis, although not statistically significant. Response rate to first generation regimens was: 37% CR (11/29), 24% PR (7/29) and 24% PD (7/29). Four patients were treated with Third generation regimens with 2 CR and 2 PR. 20 out of 25 patients with PR or CR to first line chemotherapy received mediastinal radiation therapy. More than 65% of patients had a follow up of 5 years or more. With a median follow up of 22.3 months, projected 5 year OS was 47% and for the responders the median PFS was 8,4 months. No difference in OS and PFS was observed among the three chemotherapy groups. Conclusion: Our analysis showed that response rate to first line regimens was around 60% and 25% of patients were primarily refractory to CHOP regimen. Age younger than 35 years old was associated with a better prognosis. 5 years overall survival was 45% and is in accordance with the literature. Although recent studies have demonstrated biological similarities between PMBL and Hodgkin’s Lymphoma, the prognosis of PMBL is less favorable than HL. Better understanding of the disease will help in developing more appropriate therapeutic strategies for PMBL. No significant financial relationships to disclose.

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An Escalated Dose of Bortezomib Plus Second Line Chemotherapy for the Treatment of Patients with Relapsed or Refractory Diffuse Large B-Cell Lymphoma,

Blood ◽

10.1182/blood.v118.21.3714.3714 ◽

2011 ◽

Vol 118 (21) ◽

pp. 3714-3714

Author(s):

Yongqian Jia ◽

Bing Xiang ◽

Xiaodong Wang ◽

Jianjun Li ◽

Chuan He ◽

...

Keyword(s):

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Fungus Infection ◽

Large B Cell Lymphoma ◽

One Year ◽

The One ◽

Large B Cell

Abstract Abstract 3714 Background: The non-GCB subtype of diffuse large B-cell lymphoma(DLBCL) has inferior response to rituximab based chemothrapy. Recent reports show a constitutional expression of NF-κB pathway in non-GCB subtype of DLBCL. Bortezomib, as proteasome inhibitor, has been shown a promising new agent for the treatment of DLBCL. As how the efficacy, doses and protocol of Bortezomib need to be clarified. Objective: This trial is a pilot multicenter clinical study to evaluate the efficacy and safety of an escalated dose of bortezomib based chemotherapy for the treatment of patients with relapsed or refractory non-GCB subtype of DLBCL. Patients and Materials: A total 24 pts with DLBCL were enrolled in 4 different medical centers. According to Hans' Tissue Microarray (TMA) Classification, 23 pts were diagnosed as non-GCB subtype, and 1 patient have not done the test. 16 pts had relapsed or refractory disease, while 8 pts had fail response to the first line treatment. All the patients had received Rituximab based chemotherapy previously. There were 16 male and 8 female. The patient age ranged from 19 to 73, of which the median age was 55. Methods: All patients were given bortezomib 2.0mg/m2, day 1, I.V. (intravenous injection 12 hours before chemotherapy), 5 pts were given additional dose of 0.7 mg/m2, I.V., at day 8. The combination protocols include: Bortezomib(V)+ICE(G) 13 pts; Bortezomib(V)+HyperCVAD 7 pts; Bortezomib(V)+EPOCH 3 pts; Bortezomib(V)+DHAP 1 pts. The patients were given 1 to 5.courses differently. Results: The follow-up time were 2 to18 months, with a median time of 8 months. Of 24 pts, 21 evaluable pts received more than 2 courses of therapy: 7 pts achieved complete remission (CR 33.3%), 9 pts achieved partial remission (PR 42.8%), 5 pts had no response (NR 23.8%), The overall response rate (ORR) was 76.1%. Of 16 responsive pts, the PFS were 2 to 18 months; the average PFS was 7.6 months and median PFS was 7.5 months. Up to now, 13 pts were still alive, and 7 pts were dead, and 1 pts lost follow-up. Of 7 death, 5 were caused by disease progression with 4 pts of central nervous infiltrates, 2 were caused by severe infections. The one year overall survival rate (OS) was 65%. Of all the 24 pts, 10 pts had 3 to 4 grade of myelosuppression; 1 case with severe pulmonary infection;1 case with septicemia; 1 case with skin and soft tissue infection; 1 case with fungus infection; 3 cases with herpes zoster infection; 2 cases with skin rashes; 2 cases with hypotension, 1 case with hepatic dysfunction; 1 case with neuralgia. Conclusion: Our study showed that the escalated dose of bortezomib based chemotherapy had promising response for the treatment of relapsed or refractory non-GCB originated DLBCL. Bortezomib at a single dose of 2.0mg/m2 was safe and tolerable. No acute toxicity or vital adverse events were observed. The relapse of disease in central nervous system as well as infections were relatively common and might need further study. Disclosures: No relevant conflicts of interest to declare.

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Indirect Comparison of Tisagenlecleucel and Historical Treatments for Relapsed/Refractory Diffuse Large B-cell Lymphoma

Blood Advances ◽

10.1182/bloodadvances.2021006280 ◽

2022 ◽

Author(s):

Richard T Maziarz ◽

Jie Zhang ◽

Hongbo Yang ◽

Xinglei Chai ◽

Chengbo Yuan ◽

...

Keyword(s):

B Cell ◽

Response Rate ◽

Cell Lymphoma ◽

Indirect Comparison ◽

B Cell Lymphoma ◽

Standardized Mortality Ratio ◽

Large B Cell Lymphoma ◽

Using Data ◽

Large B Cell

No head-to-head trials have compared the efficacy of tisagenlecleucel versus historical treatments for adults with relapsed or refractory diffuse large B-cell lymphoma (r/r DLBCL). This study indirectly compared the overall survival (OS) and overall response rate (ORR) associated with tisagenlecleucel, using data from the JULIET study (NCT02445248), versus historical treatments assessed in the CORAL study follow-up population. To assess treatment effects in the treated (full analysis set [FAS]) and enrolled (intent-to-treat [ITT]) study populations, the JULIET FAS vs. the CORAL follow-up FAS and JULIET ITT vs. CORAL follow-up ITT populations were separately compared. Propensity score weighting using standardized mortality ratio weight (SMRW) and fine stratification weight (FSW) was used to compare OS and ORR, adjusting for baseline confounders. The results indicated that tisagenlecleucel was associated with a lower hazard of death among the FAS (adjusted hazard ratio [95% CI], both FSW and SMRW: 0.44 [0.32, 0.59]) and ITT populations (FSW: 0.60 [0.44, 0.77], SMRW: 0.57 [0.44, 0.73]; all p<0.001). Median OS was 12.48 months (JULIET) vs. 4.34-4.40 months (CORAL) for the FAS, and 8.25 (JULIET) vs. 4.04-4.86 (CORAL) for the ITT populations. Tisagenlecleucel was associated with a significantly higher ORR compared to historical treatments among the FAS (adjusted response rate difference [95% CI], both FSW and SMRW: 36% [22%, 0.48%]; p<0.001) and among the ITT populations after SMRW adjustment (11% [0%, 22%]; p=0.043). This analysis supports that improved response and OS are achieved in r/r DLBCL patients treated with tisagenlecleucel when compared to those treated with alternative historical treatments.

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Benefit of Consolidative Radiotherapy in Patients with Limited Stage Diffuse Large B-Cell Lymphoma in the Rituximab Era

Blood ◽

10.1182/blood.v128.22.4210.4210 ◽

2016 ◽

Vol 128 (22) ◽

pp. 4210-4210

Author(s):

Nobuhiko Nakamura ◽

Yoshikazu Ikoma ◽

Yuhei Shibata ◽

Takuro Matsumoto ◽

Soranobu Ninomiya ◽

...

Keyword(s):

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Stage I ◽

Limited Stage ◽

Large B Cell Lymphoma ◽

Consolidative Radiotherapy ◽

Large B Cell

Abstract Background: Diffuse large B-cell lymphoma (DLBCL) is an aggressive type of non-Hodgkin lymphoma and the most common lymphoid neoplasm in adults. In the pre rituximab era, the standard therapy for patients with limited stage DLBCL had been three cycles of CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) followed by involved-field radiotherapy (IFRT). The addition of rituximab has revolutionized the treatment of DLBCL. Rituximab combined with CHOP (R-CHOP) has been established as the standard treatment for patients with DLBCL. However, the role of consolidative radiotherapy (RT) in the treatment of limited stage DLBCL in the rituximab era is controversial. Patients and Methods: We retrospectively analyzed 108 patients with limited stage DLBCL who received R-CHOP or R-THP-COP (rituximab plus, cyclophosphamide, pirarubicin, vincristine and prednisone) regimen between June 2004 and August 2015. We compared overall survival (OS) and progression-free survival (PFS) according to the treatment. OS was calculated from the date of initiation of chemotherapy to the date of the last follow-up or death. PFS was calculated from the date of initiation of chemotherapy to the date of progression disease, death, or last contact, whichever occurred first. Survival was estimated from Kaplan-Meier curves and compared using the log-rank test. P < 0.05 was considered statistically significant. Weighted Cox proportional hazards regression modeling with the inverse probability weighted (IPW) estimators method adjusting to propensity for RT was used to account for differences in baseline characteristics. Results: Median age at diagnosis was 66 years (19-88 years), with 61 males and 47 females. Forty-three patients (40%) had stage I, and 65 patients (60%) received consolidative RT after chemotherapy. Patients who received consolidative RT were significantly younger (65 vs 72, P < 0.01) and were more likely to have stage I disease (51% vs 23%, P < 0.01). The median number of chemotherapy cycles was 4 (range 3-8) in patients who received RT, and 6 (range 3-8) in patients who did not. Median follow-up was 4.3 years (0.3-10.9 years), and the 5-year OS (92% vs 63%, P < 0.01) and PFS (87% vs 65%, P < 0.01) were significantly higher for patients who received RT than those who did not. Using IPW adjustment, RT remained predictive of OS (HR 0.30, CI 0.13-0.72, P < 0.01) and PFS (HR 0.47, CI 0.22-0.99, P < 0.05). Conclusion: Our results suggest that consolidative RT improves OS and PFS in patients with limited stage DLBCL in the rituximab era. Although consolidative RT seems to be gradually phased out by chemotherapy alone, it is still an important treatment strategy. Disclosures No relevant conflicts of interest to declare.

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Primary Mediastinal Large B-Cell Lymphoma: Treatment Outcomes in 43 Patients.

Blood ◽

10.1182/blood.v106.11.4754.4754 ◽

2005 ◽

Vol 106 (11) ◽

pp. 4754-4754

Author(s):

Celso L. Mello ◽

Vladimir C. Lima ◽

Christiane Valadares ◽

Soares A. Fernando ◽

Carvalho A. Lopes ◽

...

Keyword(s):

B Cell ◽

First Generation ◽

Response Rate ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Third Generation ◽

First Line ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Objectives: Primary mediastinal B-cell Lymphoma (PMBL) is recognized as a separate entity in the WHO classification. Treatment for PMBL is based on a combination of conventional dose chemotherapy, high dose chemotherapy and radiation therapy. The best strategy is still undefined. We conducted a retrospective analysis of patients with PBML to identify clinical prognostic factors. Materials and Methods: Between 1989 and 2004, 43 consecutives patients treated at Hospital do Cancer AC Camargo, São Paulo, Brazil were identified and clinical and histological data were reviewed. All patients had previous diagnosis of diffuse large B-cell lymphoma, with positive CD20 on neoplastic cells. For patients with extrathoracic involvement at presentation a predominant anterior mediastinal lesion should be present. Induction chemotherapy regimens were grouped in first generation (CHOP or CHOP-like), third generation (PromaceCytabon or MACOP) and other (pediatric regimens, COP). Results: Age ranged from 16 to 82 years-old, 30 females and 13 male. Patients aged < 35 yo had better outcome compared with those older than 35 yo (5 years OS - 56% x 34%, p=0.048). Among clinical variables, female gender, stage IA-IIB, IPI 0-1, normal LDH, absence of mediastinal bulky disease were associated with better prognosis, although not statistically significant. Response rate to first generation regimens was: 37% CR (11/29), 24% PR (7/29) and 24% PD (7/29). Four patients were treated with third generation regimens with 2 CR and 2 PR. 20 out of 25 patients with PR or CR to first line chemotherapy received mediastinal radiation therapy. More than 65% of patients had a minimum time of follow up 5 years. With a median follow up of 22.3 months, projected 5 year OS was 47% and for the responders the median PFS was 8,4 months. No difference in OS and PFS was observed among the three chemotherapy groups. Conclusion: Our analysis showed that response rate to first line regimens was around 60% and 25% of patients were primarily refractory to CHOP regimen. Age younger than 35 years old was associated with a better prognosis. 5 years overall survival was 45 % and is in accordance with the literature. Although recent studies have demonstrated biological similarities between PMBL and Hodgkin’s Lymphoma, the prognosis of PMBL is less favorable than HL. Better understanding of the disease will help in developing more appropriate therapeutic strategies for PMBL.

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Concomitant Radiochemotherapy In The Treatment Of Refractory Or Locally Relapsed Diffuse Large B-Cell Lymphoma: A Single Center Retrospective Study

Blood ◽

10.1182/blood.v122.21.5114.5114 ◽

2013 ◽

Vol 122 (21) ◽

pp. 5114-5114

Author(s):

Emmanuel Gyan ◽

Alban Villate ◽

Severine Lissandre ◽

Lotfi Benboubker ◽

Martine Delain ◽

...

Keyword(s):

B Cell ◽

Conflicts Of Interest ◽

Cell Lymphoma ◽

B Cell Lymphoma ◽

Complete Response ◽

Hematological Toxicity ◽

Severe Toxicity ◽

Large B Cell Lymphoma ◽

Large B Cell

Abstract Introduction Primary refractory Diffuse Large B-Cell Lymphoma (DLBCL) as well as relapse after salvage therapy displays a poor prognosis. Salvage radiation therapy alone does not provide sufficient disease control on locally chemoresistant DLBCL. Autologous stem cell transplantation (ASCT) provides the best progression-free survival when salvaged patients are transplanted in Complete Response (CR). The objective of this study was to assess the effectiveness of CCR in locally relapsed or refractory DLBCL, followed by ASCT in responding patients. Material and methods We report the outcome of consecutive patients with locally relapsed or refractory lymphoma for which a decision of CRC was taken in a single institution. Each patient has been assessed by CT or PET-scan. The CRC regimen consisted in 3 cycles of Rituximab (375 mg/m² day 1), CDDP (30 mg/m² 3 days 1-3) and VP16 (120 mg/m² days 1-3) at 21 days intervals, with concomitant radiotherapy delivered to the residual disease sites, administrated in 2 Gy fractions per day to a total dose of 30 Gy, starting on day 1 of the second cycle. Responding patients received ASCT with a BEAM conditioning at the end of the procedure. Extra-hematological toxicity was ranked according to the Common Terminology Criteria for Adverse Events. Tumor response was evaluated according to IWG 1999 at 1 month after the last cycle of CRC, three months after ASCT if performed and during a quarterly follow-up. Results We identified 13 patients with localized chemoresistant DLBCL from January 2002 to April 2011 including 12 primary refractory forms. The median age was 56 years (20-76), 12 of 13 patients had received at least two lines of chemotherapy before inclusion with anthracycline and cisplatin. 11 patients achieved a partial response (85%) and 4 of them (31%) a complete response after the CRC. 8 (61.5%) patients were transplanted 1 month after the last cycle of CRC. 7 patients have relapsed within 6 months after the end of treatment. After a median follow-up of 37 months (range 21-125) for the surviving patients, 7 patients are alive and free of disease. The overall survival is 54%, and all surviving patients had been transplanted. No severe toxicity was reported. Conclusion CRC should be considered as an option in the therapeutic arsenal in refractory or locally relapsed DLBCL, especially in patients eligible for ASCT. Further research on CRC is warranted. Disclosures: No relevant conflicts of interest to declare.

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