Search

Patients with MYC-rearrangement positive large B-cell lymphoma (MYC+ LBCL) have an inferior prognosis following standard first-line therapy with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP) as compared to patients without MYC rearrangement. Although intensive chemotherapy regimens yield higher remission rates, toxicity remains a concern. Lenalidomide is an oral immunomodulatory drug which downregulates MYC and its target genes thereby providing support using lenalidomide as additional therapeutic option for MYC+ LBCL. A phase II trial was conducted evaluating the efficacy of lenalidomide (15 mg day 1-14) in combination with R-CHOP (R2CHOP) in newly diagnosed MYC+ LBCL patients identified through a nationwide MYC-FISH screening program. The primary endpoint was complete metabolic response (CMR) on centrally reviewed 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography (PET)-computer tomography (CT)-scan at end-of-treatment. Secondary endpoints were overall survival (OS), disease-free survival (DFS) and event-free survival (EFS). Eighty-two patients with stage II-IV MYC+ LBCL were treated with 6 cycles of R2CHOP. At EOT, 67% (confidence interval (CI) 58-75%) of the patients reached CMR. With a median follow-up of 25.4 months, 2-year estimates (95% CI) for OS, DFS, EFS were 73% (62-82%), 75% (63-84%) and 63% (52-73%) respectively. In this prospective trial for newly diagnosed MYC+ LBCL patients, we found that administering R2CHOP was safe, and yields comparable CMR and survival rates as in studies applying more intensive chemotherapy regimens. Hence, these findings offer new prospects for MYC+ LBCL patients and warrant comparison in prospective randomized clinical trials. This trial was registered at www.clinicaltrialsregister.eu (#2014-002654-39).

Background: Plasma thymus and activation-regulated chemokine is a potential biomarker for classical Hodgkin's lymphoma. To define its value as a marker to monitor treatment response, we correlated serial plasma thymus and activation-regulated chemokine levels with clinical response in newly diagnosed and relapsed classical Hodgkin's lymphoma patients., Design and Methods: Plasma was collected from 60 (39 early stage and 21 advanced stage) newly diagnosed classical Hodgkin's lymphoma patients before, during, and after treatment, and from 12 relapsed patients before and after treatment. Plasma thymus and activation-regulated chemokine levels were determined by enzyme-linked immunosorbent assay and were related to pre-treatment metabolic tumor volume, as measured by quantification of 2-[18F]fluoro-2-deoxyglucose positron emission tomography images, and to treatment response., Results: Baseline plasma thymus and activation-regulated chemokine levels correlated with stage of disease and bulky disease, and more closely with metabolic tumor volume. Response to treatment was observed among 38 of 39 early stage and 19 of 21 advanced stage patients. Reduction in plasma thymus and activation-regulated chemokine to normal range levels could be observed as early as after one cycle of chemotherapy in all responsive patients, while plasma levels remained elevated during and after treatment in the 3 non-responsive patients. Plasma thymus and activation-regulated chemokine was elevated in all 12 relapsed patients at time of relapse and remained elevated after salvage treatment in the 4 non-responsive patients., Conclusions: Baseline plasma thymus and activation-regulated chemokine levels correlate with classical Hodgkin's lymphoma tumor burden and serial levels correlate with response to treatment in patients with classical Hodgkin's lymphoma.

Background and Objectives: 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) appears to be an excellent tool for evaluating early response to chemotherapy in lymphoma patients. As only chemosensitive patients with relapsed lymphoma may benefit from ablative therapy and autologous stem cell transplantation (ASCT), PET may be used to select patients for ASCT. A prospective study was performed to investigate the optimal time point of pre-transplantation PET, using different PET-parameters., Design and Methods: Three serial whole-body attenuation-corrected FDG-PET scans were performed in 39 consecutive patients with relapsed lymphoma (28 with aggressive non-Hodgkin's lymphoma and 11 with Hodgkin's disease) eligible for second-line chemotherapy followed by ASCT: PET1 before treatment, PET2 after two cycles of induction chemotherapy and PET3 after a third cycle of chemotherapy just before ASCT in cases with an abnormal PET2. Visual analysis and standardized uptake value (SUV) parameters were obtained for each scan. The follow-up lasted a minimum of 6 months after ASCT., Results: PET2 normalized in 43% (17/39) of the patients, and PET3 normalized in 27% (6/22). Persistent abnormal FDG-uptake was observed in 41% of the patients: 15% showed partial remission and 26% stable or even progressive abnormalities. With a median follow-up of 22 months (range 6-55) 54% of all patients relapsed after ASCT. The results demonstrated that those patients who showed a complete response after the second and third cycles of chemotherapy had a 2-year progression-free survival of 71% and 58%, respectively, while those who showed no response, all relapsed shortly after ASCT. Analysis of the SUV parameters did not reveal additional information compared to that yielded by the visual assessment., Interpretation and Conclusions: Two serial PET scans predict outcome after ASCT more precisely than one interim PET in patients with relapsed lymphoma.