Low-Dose Radiotherapy in Patients with Non Hodgkin Lymphoma

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4875-4875
Author(s):  
Dulcineia Pereira ◽  
Sergio Pereira Chacim ◽  
Andre Soares ◽  
Edgar Mesquita ◽  
Ana Espirito-Santo ◽  
...  

Abstract Abstract 4875 Background: Some studies have showed high activity for low-dose radiotherapy (LDRT) in low-grade Non-Hodgkin Lymphoma (NHL). However, this therapeutic approach is often forgotten and other approaches are used - chemotherapy and/or conventional radiotherapy - associated with greater toxicity. The efficacy of total body LDRT (1.5–2 Gy, fractions 0.1–0.25 Gy in 2 – 5 times a week) in disseminated disease is associated with 10 year progression free survival (PFS) of 15 – 25%, with response rates of 70 – 90% (Gérard et al., IJ Radiation Oncology 2010; 78), despite hematologic toxicity and leukemogenic effects. Although its mechanism of action is unknown, its effectiveness has been confirmed (Jones et al., Cancer 1973; 32) suggesting that low dose radiation induces localized lymphocytes apoptosis that can trigger local and systemic benefits. More recently, LDRT was used in palliative treatment for patients with localized disease (4Gy into two fractions, for 3 days) with a low toxicity, and with an objective response (partial or complete) in 24/37 patients, 89% (G Ganem et al., Hematol Oncol1997; 42). Objectives: To assess the response to treatment with LDRT. Explore the predictive factors of response. Determine the progression-free survival (PFS) after LDRT. We will present PFS after LDRT and compare PFS in second line treatment: LDRT vs convencional chemotherapy. Methods: Retrospective study of 44 patients with new or recurrent NHL, treated with LDRT (4Gy in 2 fractions) in 1stor more lines, in a cancer care centre between 2004 and 2011. All transformed lymphomas were excluded (4 patients), as well all diagnosis that weren't centrally reviewed. Patients with complete resolution of the disease according to clinical and/or image studies were considered to have achieved complete response (CR). Results: We identified 40 patients undergoing LDRT, with a median follow-up of 69,5 months after LDRT ([28–87]). 52,5% (n = 21) were male, median age at the time of LDRT was 69 years ([31–85]). 75% of patients (n = 30) had follicular NHL, 12,5% (n = 5) Mantle cell NHL, 10% (n = 4) Marginal Zone NHL and 2,5% (n = 1) lymphoplasmacytic lymphoma. The median numbers of lines of chemotherapy completed before LDRT were 2 lines ([0–5]). There wasn't any impact on PFS on using Rituximab containing regimens after LDRT (p> 0,05). The overall response rate to LDRT was 92,5% (n = 37): 42,5% (n = 17) achieved complete response (CR), 50% (n = 20) partial response (PR) and 7,5% (n = 3) had disease progression. There weren't any treatment related toxicities, nor was histological transformation recorded after treatment with LDRT. The logistic regression analysis showed that irradiated areas with dimension <40mm are an independent predictive factor of response (p <0,031, 95% CI [1,268-133,285]). We find a median PFS of 4 months ([0–72]) for patients that went on LDRT, and 50% of these patients relapsed after a median 5 months ([0–35]). 56,5% (n = 13) showed relapse at the same location of the irradiated area. Patients who have completed one chemotherapy scheme after relapsing following LDRT, showed a rate of 6 months-PFS of 50% such as the patients that have done a second LDRT treatment. Concerning follicular NHL patients who relapsed after 1st line conventional chemotherapy, 43,8% (n = 7) were treated with LDRT and 56,2% (n = 9) were treated with conventional 2nd line chemotherapy. Comparing these two groups of patients, there weren't any difference for PFS for both groups (mean 9,5 vs 9 months p> 0,05, for LDRT vs 2ndline chemotherapy), for equal overall survival. Conclusion: LDRT is an effective treatment for patients with relapsed or recurrent advanced stage NHL. We can obtain high response rates with negligible toxicity. In the treatment of first relapse, PFS is similar when using LDRT or 2nd line chemotherapy. Considering that Rituximab promotes a synergistic effect with LDRT-induced apoptosis and decrease the cell turnover (Skvortsova I et al., J Radiat Res (Tokyo) 2006), comparative studies with conventional chemotherapy regimens should be promoted. Treatment with conventional radiotherapy should be used in patients with relapsed low-stage and localized disease, having curative intention or locally controlling involved areas. Disclosures: No relevant conflicts of interest to declare.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 4040-4040 ◽  
Author(s):  
Heinz-Josef Lenz ◽  
Sara Lonardi ◽  
Vittorina Zagonel ◽  
Eric Van Cutsem ◽  
M. Luisa Limon ◽  
...  

4040 Background: In the phase 2 CheckMate 142 trial, NIVO + low-dose IPI had robust, durable clinical benefit and was well tolerated as 1L therapy for MSI-H/dMMR mCRC (median follow-up 13.8 months [mo; range, 9–19]; Lenz et al. Ann Oncol 2018;29:LBA18). Longer follow-up is presented here. Methods: Patients (pts) with MSI-H/dMMR mCRC and no prior treatment for metastatic disease received NIVO 3 mg/kg Q2W + low-dose IPI 1 mg/kg Q6W until disease progression or discontinuation. The primary endpoint was investigator-assessed (INV) objective response rate (ORR) per RECIST v1.1. Results: In 45 pts with median follow-up of 29.0 mo, ORR (95% CI) increased to 69% (53–82) (Table) from 60% (44.3–74.3); complete response (CR) rate increased to 13% from 7%. The concordance rate of INV and blinded independent central review was 89%. Median duration of response (DOR) was not reached (Table). Median progression-free survival (PFS) and overall survival (OS) were not reached, and 24-mo rates were 74% and 79%, respectively (Table). Nineteen pts discontinued study treatment without subsequent therapy. An analysis of tumor response post discontinuation will be presented. Ten (22%) pts had grade 3–4 treatment-related adverse events (TRAEs); 3 (7%) had grade 3–4 TRAEs leading to discontinuation. Conclusions: NIVO + low-dose IPI continued to show robust, durable clinical benefit with a deepening of response, and was well tolerated with no new safety signals identified with longer follow-up. NIVO + low-dose IPI may represent a new 1L therapy option for pts with MSI-H/dMMR mCRC. Clinical trial information: NTC02060188 . [Table: see text]


2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 7500-7500 ◽  
Author(s):  
Ian Flinn ◽  
Richard van der Jagt ◽  
Julie E. Chang ◽  
Peter Wood ◽  
Tim E. Hawkins ◽  
...  

7500 Background: BRIGHT, a phase 3, open-label, noninferiority study comparing efficacy and safety of bendamustine plus rituximab (BR) vs rituximab plus cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) or rituximab with cyclophosphamide, vincristine and prednisone (R-CVP) in treatment-naive patients (pts) with indolent non-Hodgkin lymphoma (iNHL) or mantle cell lymphoma (MCL), showed that the complete response rate for first-line BR was statistically noninferior to R-CHOP/R-CVP ( Blood 2014). Pts were monitored for ≥5 years (yr) to assess the overall effect of BR or R-CHOP/R-CVP in a controlled clinical setting. This analysis reports the time-to-event variables of the 5-yr follow-up (FU) study. Methods: Pts with iNHL or MCL randomized to 6-8 cycles of BR or R-CHOP/R-CVP underwent complete assessments at end of treatment, then were monitored regularly. Progression-free survival (PFS), event-free survival (EFS), duration of response (DOR) and overall survival (OS) were compared using a stratified log-rank test. Results: Of 447 randomized pts, 224 received BR, 104 R-CHOP, and 119 R-CVP; 419 entered the FU. The median FU time was 65.0 and 64.1 months for BR and R-CHOP/R-CVP, respectively. The 5-yr PFS rate was 65.5% (95% CI 58.5-71.6) and 55.8% (48.4-62.5), and OS was 81.7% (75.7-86.3) and 85% (79.3-89.3) for BR and R-CHOP/R-CVP, respectively. The hazard ratio (95% CI) for PFS was 0.61 (0.45-0.85; P= .0025), EFS 0.63 (0.46-0.84; P= .0020), DOR 0.66 (0.47-0.92; P= .0134), and OS 1.15 (0.72-1.84; P= .5461) comparing BR vs R-CHOP/R-CVP. Similar results were found in iNHL [PFS 0.70 (0.49-1.01; P= .0582)] and MCL [PFS 0.40 (0.21-0.75; P= .0035)], with the strongest effect in MCL. Use of R maintenance was similar, 43% in BR and 45% in R-CHOP/R-CVP. B was included as second-line in 27 (36%) of the 75 pts requiring therapy who originally received R-CHOP/R-CVP. Comparable safety profiles with expected adverse events were observed in the FU study in BR vs R-CHOP/R-CVP. Conclusions: The long-term FU of the BRIGHT study has confirmed that PFS, EFS, and DOR were significantly better for BR, and OS was not statistically different between BR and R-CHOP/R-CVP. The safety profile was as previously reported. Clinical trial information: NCT00877006.


Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4962-4962
Author(s):  
Fan Zhou ◽  
Lieping Guo ◽  
Haotian Shi ◽  
Chenhui Lin ◽  
Jian Hou

Abstract Abstract 4962 Objective To assess the efficacy and tolerability of continuous low-dose cyclophosphamide and prednisone regimen (CP) as a salvage therapy for multiple myeloma (MM). Method The CP regimen consisted of oral cyclophosphamide at 50 mg and prednisone at 15 mg daily. A total of 27 consecutive patients received the CP regimen: 19 patients had severe comorbid conditions; 8 were unwilling to continue conventional chemotherapy due to severe infection associated with conventional treatment. All patients had received 1-4 chemotherapeutic regimens prior to the current study. Result The overall response rate (complete remission, very good partial response, and partial response) was 66.7%. The median time to response was 2 months. In the patients who responded to the treatment, the median progression-free survival has not been reached. In the non-responding patients, the median progression-free survival was 4 months. In patients with severe comorbid conditions and unwilling to accept conventional chemotherapy because of severe infection, the physical conditions improved significantly. Conclusion Continuous low-dose CP regimen is an effective and well-tolerated salvage therapy for MM. Disclosures No relevant conflicts of interest to declare.


2021 ◽  
pp. 20210012
Author(s):  
Marzia Cerrato ◽  
Erika Orlandi ◽  
Angelisa Vella ◽  
Sara Bartoncini ◽  
Giuseppe C Iorio ◽  
...  

Objectives: To investigate the efficacy of a schedule of low dose radiotherapy (LDRT) with 4 Gy (2 Gy x 2) in a cohort of unselected MALT or MZL patients. Methods: We retrospectively collected all patients receiving LDRT, either for cure or palliation, for a stage I–IV histologically proven MALT or MZL between 2016 and 2020. Response to LDRT was evaluated with the Lugano criteria. Local control (LC), distant relapse-free survival (DRFS), progression-free survival (PFS) and overall survival (OS) were stratified for treatment intent (curative vs palliative) and estimated by the Kaplan Meier product-limit. Results: Among 45 consecutive <>enrolled patients with a median age of 68 years (range 22–86), 26 (58%) were female. Thirty-one patients (69%) with a stage I–II disease received LDRT as first line therapy and with a curative intent. Overall response rate was 93%, with no significant difference among curative and palliative intent. With a median follow-up of 18 months, LC, DRFS, PFS and OS at 2 years were 93%, 92%, 76% and 91%, respectively, in the overall population. Patients receiving curative LDRT had a better PFS at 2 years (85% vs 54%, p < 0.01) compared to patients receiving palliative treatment. LDRT was well tolerated in all patients, without any significant acute or chronic side-effect. Conclusions: LDRT is effective and well tolerated in patients affected with MALT or nodal MZL, achieving high response rates and durable remission at 2 years. Advances in knowledge: This study shows the efficacy of LDRT in the treatment of MALT and MZL.


2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 13578-13578
Author(s):  
C. Gennatas ◽  
V. Michalaki ◽  
S. Gennatas ◽  
A. Kondi-Paphiti ◽  
D. Voros ◽  
...  

13578 Background: Capecitabine is an oral fluoropyrimidine with superior activity and safety compared with bolus 5-FU/LV in metastatic colorectal cancer (CRC). The aim of this study was to evaluate the efficacy and safety of a combination of capecitabine and oxaliplatin as first-line chemotherapy in patients with advanced CRC. Methods: Fourty-six patients (26 men and 20 women) with metastatic CRC entered this study. All patients were treated with capecitabine (1,000mg/m2 p.o.twice daily, days 1–14) and oxaliplatin (130mg/m2 on day 1). Cycles were repeated every 21 days until disease progression or unacceptable toxicity. Baseline characteristics: Median age 61 years (range 32–74), main sites of metastasis: Liver 32 patients (70%), liver and lungs 4 patients (9%), lungs 3 patients (6%), other sites 7 patients (15%). Results: 2 patients (4%) achieved complete response (CR), 17 patients (37%) achieved partial response (PR) and 7 patients (15%) attained stable disease (SD). With a median follow-up of 22 months the progression free survival was 7.5 months and overall survival was 19.0 months. All patients were assessable for toxicities. The most commonly encountered adverse events were from the gastrointestinal system (all grades 48%, grade 3, 6%). Neither toxic death nor life-threatening febrile neutropenia were reported. Conclusions: The combination of capecitabine and oxaliplatin is a convenient regimen in patients with advanced CRC that is associated with considerable efficacy and limited toxicity. No significant financial relationships to disclose.


Author(s):  
Brandon S. Imber ◽  
Karen W. Chau ◽  
Jasme Lee ◽  
Jisun Lee ◽  
Dana L. Casey ◽  
...  

Radiotherapy plays an important role in managing highly radiosensitive, indolent non-Hodgkin lymphomas (iNHL), such as follicular lymphoma (FL) and marginal zone lymphoma (MZL). While the standard of care for localized iNHL remains 24Gy, de-escalation to very low dose radiotherapy (VLDRT) of 4Gy further reduces toxicities and treatment duration. Use of VLDRT outside of palliative indications remains controversial, however, we hypothesize that it may be sufficient for most lesions. We present the largest single institution VLDRT experience of adult patients with FL and MZL treated between 2005 and 2018 (n=299 lesions; 250 patients) utilizing modern principles including PET staging and involved site radiotherapy (ISRT). Outcomes include best clinical/radiographic response between 1.5-6 months post-VLDRT, and cumulative incidence of local progression (LP) with only death as competing risk. Post-VLDRT, the overall response rate was 90% for all treated sites with 68% achieving complete response (CR). With median follow-up of 2.4 years, the 2-year cumulative incidence of LP was 25% for the entire cohort and 9% after frontline VLDRT treatment for potentially curable, localized disease. Lesion size &gt;6cm was associated with lower odds of attaining a CR and greater risk of LP. There was no suggestion of inferior outcomes for potentially curable lesions. Given the clinical versatility of VLDRT, we propose to implement a novel, incremental, adaptive ISRT strategy where patients will be treated initially with VLDRT, reserving full dose treatment for those who fail to attain a CR.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 788-788 ◽  
Author(s):  
Joerg Schubert ◽  
Marita Ziepert ◽  
Eva Lengfelder ◽  
Martin Mohren ◽  
Norma Peter ◽  
...  

Abstract Background: While the CHOP regimen is widely accepted standard chemotherapy regimen of care for aggressive lymphomas, the optimal number of chemotherapy cycles for the treatment of aggressive lymphomas has not been determined. Since RICOVER-60 is the first randomized comparison between 6 and 8 cycles of chemotherapy, it allowed to analyze whether 8 cycles are better than 6 in patients with poor prognosis and/or those achieving less than a complete response after 4 cycles of chemotherapy. Methods: In the RICOVER-60 trial, 1222 elderly patients (61–80 years, stages I–IV) were randomized to receive 6 or 8 cycles of CHOP-14 with or without rituximab given on days 1, 15, 29, 43, 57, 71, 85, and 99. Radiotherapy was planned to sites of initial bulk and/or extranodal involvement. Results: In a multivariate analysis adjusted for prognostic factors using 6xCHOP-14 without rituximab as the reference, all intensified regimens improved event-free survival. Compared to 6xCHOP-14, progression-free survival (PFS) improved after 6xR-CHOP-14 and 8xR-CHOP, while overall survival (OS) improved only after 6xR-CHOP-14 (Pfreundschuh et al., 2006, Blood 108: 64a, Abstract #205). Since 8 cycles of chemotherapy were not better than 6 in the overall RICOVER-60 population, we searched for subgroups who might have a benefit from the two additional cycles of chemotherapy. The outcome after 6 cycles was at least as good as 8 cycles, in any risk group according to IPI. Compared to patients in CR after 4 cycles (n=261), patients in PR after 4 cycles (n=459) had a significantly worse 3-year PFS (63% vs. 75%; p=.001) and OS (69% vs. 84%; p=0.001), while for patients in CRu (n=276) this applied to PFS (68% vs. 76%; p=0.043), but not to OS (78% vs. 84%; p=0.125). Among patients with mid-therapy CRu, the 3-year progression free rates receiving 6 cycles (6x-CHOP-14: 65%, 6xR-CHOP-14: 72%) and those receiving 8 cycles (8xCHOP-14: 63%; 8xR-CHOP-14: 71%) were not different (p=0.601 and p=0.815 without and with rituximab, respectively). The same was true with respect to overall survival (6xCHOP-14: 82%; 8xCHOP-14: 70%; 6xR-CHOP-14: 80%; 8xR-CHOP-14: 80%; p=0.422 and p=0.759 without and with rituximab, respectively). Conclusion: Patients in CR after 4 cycles of therapy have a better outcome than those in CRu and PR at mid-therapy, with no difference between patients who received 6 and 8 cycles of (R−)CHOP-14. Response-adapted assignment of 8 cycles instead of 6 does not compensate for the worse prognosis of patients achieving less than a CR after 4 cycles. Response-adapted assignment of the number of chemotherapy cycles - either with or without rituximab - is not supported by our data.


2017 ◽  
Vol 24 (5) ◽  
pp. 361 ◽  
Author(s):  
W.M. Jose ◽  
K. Pavithran ◽  
T.S. Ganesan

Purpose We assessed response to treatment, toxicity, time to progression, progression-free survival, and overall survival in patients newly diagnosed with multiple myeloma who were ineligible for or unwilling to undergo transplantation and who were treated with a combination of lenalidomide and low-dose dexamethasone for a fixed 6 cycles in a resource-constrained environment.Methods This pragmatic study, conducted in a single tertiary cancer centre in South India, enrolled patients from May 2009 till April 2011. Treatment included lenalidomide 25 mg daily for 21 days, with dexamethasone 40 mg on days 1, 8, 15, and 22 of a 28-day cycle, for 6 cycles. Response was evaluated after the 3rd and 6th cycles of treatment. All patients were followed for 5 years.Results The study enrolled 51 patients. Median age in the group was 61 years (range: 38–76 years). Immunoglobulin G or A myeloma constituted 70.6% of the diagnoses, and light-chain myeloma constituted 29.4%. Stages i, ii, and iii (International Staging System) disease constituted 21.4%, 28.6%, and 50% of the diagnoses respectively. All patients were transplantation-eligible, but 34 (66.7%) refused for economic reasons. After treatment, 19.6% of the patients achieved a stringent complete response; 35.3%, a complete response; 5.9%, a very good partial response; and 29.4%, a partial response, for an overall response rate of 90.2%. Stable disease was seen in 3.9% of patients, and progressive disease, in 5.9%. Grade 3 or greater nonhematologic and hematologic toxicity occurred in 35.2% and 11.7% of patients respectively. Pulmonary embolism occurred in 1 patient. No patient experienced deep-vein thrombosis or peripheral neuropathy. The median follow-up duration was 66 months. All patients experienced disease progression. Median progression-free survival was 16 months. In 10 patients, re-challenge with lenalidomide and dexamethasone achieved a second complete response. At the time of writing, 19 patients had died. The overall survival rate at 5 years was 62.74%. Median overall survival is not yet reached.Conclusions In a resource-constrained setting, lenalidomide with low-dose dexamethasone is an effective treatment with acceptable toxicity in patients newly diagnosed with multiple myeloma and not planned for transplantation. Complete responses were significantly more frequent than reported in the Western literature. Occurrence of clinical deep-vein thrombosis was rare, but hyperglycemia was common. An abbreviated course of treatment is suboptimal in multiple myeloma. Maintenance regimens should be advocated.


2019 ◽  
Vol 21 (Supplement_6) ◽  
pp. vi232-vi232 ◽  
Author(s):  
Samantha Reiss ◽  
Prakirthi Yerram ◽  
Lisa Modelevsky ◽  
Christian Grommes

Abstract BACKGROUND Primary Central Nervous System Lymphoma (PCNSL) is an aggressive rare non-Hodgkin lymphoma. Prognosis is particularly poor for relapsed/recurrent (R/R) patients with no established treatment modality. Methotrexate/BCNU/Teniposide/Prednisone with or without rituximab has efficacy in newly diagnosed PCNSL. Here, we report efficacy and toxicity of RMBVP for the treatment of R/R PCNSL. METHODS This retrospective study at MSKCC included PCNSLs treated with MBVP for R/R disease between 5/2009 and 5/2019. Methotrexate (3.5 g/m2; day 1 and 15), etoposide (100 mg/m2; day 2), BCNU (100 mg/m2; day 3), prednisone (60 mg/m2/day; day 1–5) and rituximab (500 mg/m2; day 0 and 14) were given in 28-day cycles. Granulocyte colony-stimulating factor support was given for 5 days in between doses of chemotherapy. RESULTS Thirty patients received MBVP; 27 (90%) received RMBVP with a median of 2 cycles given (0.5–5). Median age was 66 years (23–81); median KPS was 70 (30–90); 14 (46.7%) were women. Median prior lines of therapy were 2 (1–5); all received prior methotrexate. Median time from last treatment was 1 month (0–88.3; 21 (70%) < 12 months). Of twenty-nine evaluable patients for response, 23 (76.7%) had a response (9 complete response (CR) (30%), 5 CR-unconfirmed (16.7%), 8 partial response (26.7%), 1 stable disease (3%)). At a median follow up of 14.2 months, median progression free survival (PFS) was 15.6 months and median overall survival was not reached. Median PFS was poorer for patients with < 12 months since last chemotherapy, 10.1 vs 60.6 months. Rates of serious (grade 3 or 4) neutropenia, anemia, thrombocytopenia and transaminitis were 20%, 20%, 16.7%, and 16.7%, respectively. One patient experienced grade 3 nephrotoxicity. No treatment related mortalities occurred. CONCLUSIONS RMBVP is a tolerable treatment option for R/R PCNSL, particularly in those with recurrent disease.


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