Modeling combined chemo- and immunotherapy of high-grade non-Hodgkin lymphoma.
LIFE - Leipzig Research Center for Civilization Diseases, Genetical Statistics and Systems Biology

Abstract (Expand)

Moderate, but not massive intensification of CHOP-21 improves outcome in aggressive non-Hodgkin lymphoma. Adding immunotherapy with Rituximab was a break-through, but levels differences in chemotherapy. … Ongoing trials attempt to optimize R-CHOP type regimens. We present a mathematical model of chemo-immunotherapy to explain published and aiming at predicting future trials comparing R-CHOP variants. We hypothesize that, for cure, the immune system must dominate residual tumor cells at the end of treatment. Chemotherapy reduces both tumor and immune cells. Rituximab immunotherapy boosts the immune response. We translate this reasoning into a differential equations model. Model parameters are estimated using data of randomized clinical trials in elderly patients. The model explains observed hazard ratios between treatments. It explains why too intense chemotherapy could be detrimental. The model is validated predicting six published independent studies. As an application, we varied treatment schedules and predict that current R-CHOP variants have only limited optimization potential.

Authors: K. Rosch, M. Scholz, D. Hasenclever

Date Published: 16th Dec 2015

Publication Type: Not specified

Human Diseases: lymphoma

Obesity negatively impacts outcome in elderly female patients with aggressive B-cell lymphomas treated with R-CHOP: results from prospective trials of the German high grade non-Hodgkin's lymphoma trial group.
GLA - German Lymphoma Alliance

Abstract (Expand)

To study if obesity is a risk factor in elderly patients (>60 years) with aggressive B-cell lymphoma, the outcomes of 576 elderly patients treated with rituximab in the RICOVER-60 trial were analysed … in a retrospective study with regard to body mass index (BMI) and gender. Of the 576 patients, 1% had low body weight (BMI < 18.5), 38% were normal weight (18.5 </= BMI < 25), 42% were overweight (25 </= BMI < 30) and 19% were obese (BMI >/= 30). Event-free (EFS), progression-free (PFS) and overall survival (OS) according to BMI showed no significant differences for all and for male patients. EFS (P = 0.041), PFS (P = 0.038) and OS (P = 0.031) were significantly better for female non-obese patients. A multivariate analysis adjusted for International Prognostic Index risk factors confirmed these results, with the following hazard ratios (HR) for obesity (BMI >/= 30) for EFS/PFS/OS: all patients - 1.4/1.4/1.4 (not significant); male patients - 1.2/1.2/1.0 (not significant) and female patients - 1.7 (P = 0.032)/1.9 (P = 0.022)/2.0 (P = 0.017). In conclusion, obesity is a risk factor that influences treatment outcome in elderly female patients with aggressive B-cell lymphoma treated with R-CHOP (rituximab + cyclophosphamide, doxorubicin, vincristine, prednisolone). The inferior outcomes in obese female patients may be due to faster rituximab clearance in obese females.

Authors: K. Hohloch, B. Altmann, M. Pfreundschuh, M. Loeffler, N. Schmitz, F. Zettl, M. Ziepert, L. Trumper

Date Published: 2nd Dec 2017

Publication Type: Not specified

Human Diseases: obesity, B-cell lymphoma

Refractory or relapsed aggressive B-cell lymphoma failing (R)-CHOP: an analysis of patients treated on the RICOVER-60 trial.
GLA - German Lymphoma Alliance

Abstract (Expand)

Background: The prognosis of elderly patients with aggressive B-non-Hodgkin's lymphoma after first lymphoma-related treatment failure (TF-L) is not well described. Methods: We analysed patient … characteristics including the presence of MYC rearrangements and MYC-expression immunohistochemistry (IHC) at diagnosis and modalities of salvage therapy and their impact on the prognosis of patients between 61 and 80 years who had been treated on the RICOVER-60 trial. Results: TF-L occurred in 301 of the 1222 (24.6%) patients; 297 patients could be analysed. Prognosis was extremely poor in patients with primary progressive disease or early relapse (</=12 months) with median survivals of 3.3 and 6.4 months. Survival after TF-L was significantly lower in patients pretreated with R-CHOP compared with CHOP (23.0% versus 36.4% at 2 years, P = 0.016). In patients with MYC translocation at diagnosis Rituximab reduced the risk of TF-L from 58.8% to 26.3%. Survival after TF-L was significant longer for patients after CHOP without MYC translocations (31.8% versus 0% at 2 years, P < 0.001) or negative MYC-IHC (41.0% versus 16.8% at 2 years, P = 0.017) but not after R-CHOP. 224 patients (75.4%) received salvage therapy. Rituximab was part of salvage therapy in 57.4% and improved 2-year survival rate from 20.7% to 46.8% (P < 0.001). The benefit of R was significant after first-line CHOP [2-year overall survival (OS) 49.6% versus 19.1%, P < 0.001] as well as after R-CHOP (2-year OS 33.1% and 22.5%, P = 0.034). For patients pretreated with R-CHOP long-term survival was below 15% regardless of the treatment chosen. Conclusion: MYC rearrangement and IHC are adverse prognostic factors after TF-L for CHOP treated patients, rituximab as part of first-line therapy reduced the effects of MYC-break. Rituximab improves results of any type of salvage therapy; however, survival after progression/relapse of aggressive B-cell lymphoma in elderly patients pretreated with (R)-CHOP is poor regardless of treatment chosen.

Authors: B. Glass, A. J. Dohm, L. H. Truemper, M. Pfreundschuh, A. Bleckmann, G. G. Wulf, A. Rosenwald, M. Ziepert, N. Schmitz

Date Published: 1st Dec 2017

Publication Type: Not specified

Human Diseases: B-cell lymphoma

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