Sequential Dose-Dense R-CHOP Followed by ICE Consolidation (MSKCC Protocol 01-142) without Radiotherapy for Patients with Primary Mediastinal Large B Cell.

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Sequential Dose-Dense R-CHOP Followed by ICE Consolidation (MSKCC Protocol ) without Radiotherapy for Patients with Primary Mediastinal Large B Cell Lymphoma Moskowitz C et al. Proc ASH 2010;Abstract 420.

Background Primary mediastinal large B cell lymphoma (PMBCL) is a distinct subtype of diffuse large B cell lymphoma (DLBCL) that is more closely related to Hodgkin lymphoma. –More common in women –Median age ~ 30 years –Represents a high percentage of aggressive lymphomas in patients under 40 years of age –Bulky mediastinal disease is common Combined chemotherapy and radiation therapy have been the mainstay of treatment. Radiation therapy is associated with a risk of secondary breast cancer and coronary artery disease. Protocols that do not use radiation therapy are therefore desirable, provided they maintain efficacy outcomes. Moskowitz C et al. Proc ASH 2010;Abstract 420.

Moskowitz C et al. J Clin Oncol 2010;28: MSKCC Study Schema: Primary Mediastinal B-Cell Lymphoma Subgroup FDG-PET R-CHOP-14 X 4 Negative Positive ICE x 3 Biopsy ICE x 2 R-ICE x 1 Positive Negative Observation Autotransplant Eligibility (N = 54)* Primary mediastinal B-cell lymphoma (PMBCL) * Not all patients were treated per on-study protocol

Patient Characteristics Characteristic N = 54 Median Age33 Female56% Elevated LDH87% Karnofsky Performance Status < 80%24% Stage IV Disease57% Extranodal Disease74% Bulky Mediastinal Disease ≥ 10cm67% Moskowitz C et al. Proc ASH 2010;Abstract 420.

Survival: RICE versus ICE Consolidation With permission from Moskowitz C et al. Proc ASH 2010;Abstract 420. Time in Months PFS Probability OS Probability Progression Free Survival: RICE vs ICEOverall Survival: RICE vs ICE RICE pts n = 17; 15 censored ICE pts n = 37; 28 censored Log Rank Test: p =.829Log Rank Test: p =.245 RICE pts n = 17; 17 censored ICE pts n = 37; 31 censored

Interim FDG-PET With permission from Moskowitz C et al. Proc ASH 2010;Abstract /54 patients had an FDG-PET interim scan 23 patients had a +FDG-PET (SUV > 3.0) – All + scans had uptake > mediastinal blood pool 14 patients had a biopsy due to +FDG-PET – 11/14 had a negative biopsy Change in SUV between initial and interim scan (cutoff of >66% as being favorable) also did not predict outcome (p = 0.216) PFS Probability Time in Months Log Rank Test: p =.414 PET Positive Pts: n = 23; censored = 17 PET Negative Pts: n = 28; censored = 23 PFS Interim FDG-PET

Moskowitz C et al. Proc ASH 2010;Abstract 420. Outcome of Patients with Events Eleven patients had an event after treatment –One patient died from AML (6 years post-treatment) –One patient was lost to follow-up — died of unknown causes (4 years post-treatment) –Nine patients have relapsed Six patients received HDT/ASCT -Five patients are progression free after salvage therapy and autotransplant, which included pretransplant radiation to the mediastinum -One patient did not respond to ASCT and died of disease progression Three patients died from PMBCL secondary to primary refractory disease

Author Conclusions The MSKCC dose-dense R-CHOP/ICE program is highly effective in PMBCL. Importantly, 50% of patients with progression can be salvaged with a radiation-based transplant. Based on these results, an interim FDG-PET scan is not warranted as it provides no useful information in this subset of patients with DLBCL. Moskowitz C et al. Proc ASH 2010;Abstract 420.

Investigator Comment on Sequential Dose-Dense R-CHOP Followed by ICE Consolidation without Radiation Therapy for Patients with Primary Mediastinal Large B-Cell Lymphoma This is a follow-up to the study that we published in the JCO, in which we treated advanced-stage diffuse large B-cell lymphoma in 98 patients and had an overall survival rate of 79 percent at a median of 44 months follow-up. This presentation is from patients with primary mediastinal large B-cell lymphoma (PMBCL) and is the largest study reported in this entity without consolidative radiation therapy. Currently, most patients with PMBCL treated in the community receive R-CHOP followed by radiation therapy. Most physicians would prefer not to administer mediastinal radiation therapy, particularly to a young woman. This study shows that radiation therapy is not necessary and it could be reserved for patients who experience relapse. Treated this way, without initial consolidative radiation therapy, the issues of secondary breast cancer and long-term coronary artery disease could be prevented. Interview with Craig Moskowitz, MD, January 3, 2011