An international phase II trial of single-agent lenalidomide for relapsed or refractory aggressive B-cell non-Hodgkin's lymphoma

Abstract Background Lenalidomide is an immunomodulatory agent with antitumor activity in B-cell malignancies. This phase II trial aimed to demonstrate the safety and efficacy of lenalidomide in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), mantle cell lymphoma (MCL), follicular grade 3 lymphoma (FL-III), or transformed lymphoma (TL). Methods Patients received oral lenalidomide 25 mg on days 1–21 every 28 days as tolerated or until progression. The primary end point was overall response rate (ORR). Results Two hundred and seventeen patients enrolled and received lenalidomide. The ORR was 35% (77/217), with 13% (29/217) complete remission (CR), 22% (48/217) partial remission, and 21% (45/217) with stable disease. The ORR for DLBCL was 28% (30/108), 42% (24/57) for MCL, 42% (8/19) for FL-III, and 45% (15/33) for TL. Median progression-free survival for all 217 patients was 3.7 months [95% confidence interval (CI) 2.7–5.1]. For 77 responders, the median response duration lasted 10.6 months (95% CI 7.0–NR). Median response duration was not reached in 29 patients who achieved a CR and in responding patients with FL-III or MCL. The most common adverse event was myelosuppression with grade 4 neutropenia and thrombocytopenia in 17% and 6%, respectively. Conclusion Lenalidomide is well tolerated and produces durable responses in patients with relapsed or refractory aggressive non-Hodgkin's lymphoma

A phase II trial of the oral mTOR inhibitor everolimus in relapsed aggressive lymphoma

The phosphatidylinositol 3-kinase signal transduction pathway members are often activated in tumor samples from patients with non-Hodgkin's lymphoma (NHL). Everolimus is an oral agent that targets the raptor mammalian target of rapamycin (mTORC1). The goal of this trial was to learn the antitumor activity and toxicity of single-agent everolimus in patients with relapsed/refractory aggressive NHL. Patients received everolimus 10 mg PO daily. Response was assessed after two and six cycles, and then every three cycles until progression. A total of 77 patients with a median age of 70 years were enrolled. Patients had received a median of three previous therapies and 32% had undergone previous transplant. The overall response rate (ORR) was 30% (95% confidence interval: 20–41%), with 20 patients achieving a partial remission and 3 a complete remission unconfirmed. The ORR in diffuse large B cell was 30% (14/47), 32% (6/19) in mantle cell and 38% (3/8) in follicular grade 3. The median duration of response was 5.7 months. Grade 3 or 4 anemia, neutropenia and thrombocytopenia occurred in 14, 18 and 38% of patients, respectively. Everolimus has single-agent activity in relapsed/refractory aggressive NHL and provides proof-of-concept that targeting the mTOR pathway is clinically relevant

Long-term complete responses after 131I-tositumomab therapy for relapsed or refractory indolent non-Hodgkin's lymphoma

We present the long-term results of 18 chemotherapy relapsed indolent (N=12) or transformed (N=6) NHL patients of a phase II anti-CD20 131I-tositumomab (Bexxar®) therapy study. The biphasic therapy included two injections of 450 mg unlabelled antibody combined with 131I-tositumomab once as dosimetric and once as therapeutic activity delivering 75 or 65 cGy whole-body radiation dose to patients with normal or reduced platelet counts, respectively. Two patients were not treated due to disease progression during dosimetry. The overall response rate was 81% in the 16 patients treated, including 50% CR/CRu and 31% PR. Median progression free survival of the 16 patients was 22.5 months. Median overall survival has not been reached after a median observation of 48 months. Median PFS of complete responders (CR/CRu) has not been reached and will be greater than 51 months. Short-term side effects were mainly haematological and transient. Among the relevant long-term side effects, one patient previously treated with CHOP chemotherapy died from secondary myelodysplasia. Four patients developed HAMA. In conclusion, 131I-tositumomab RIT demonstrated durable responses especially in those patients who achieved a complete response. Six of eight CR/CRu are ongoing after 46–70 months

Radioimmunotherapy of B-cell lymphoma with radiolabelled anti-CD20 monoclonal antibodies

CD20 has proven to be an excellent target for the treatment of B-cell lymphoma, first for the chimeric monoclonal antibody rituximab (Rituxan™), and more recently for the radiolabelled antibodies Y-90 ibritumomab tiuxetan (Zevalin™) and I-131 tositumomab (Bexxar™). Radiation therapy effects are due to beta emissions with path lengths of 1–5 mm; gamma radiation emitted by I-131 is the only radiation safety issue for either product. Dose-limiting toxicity for both radiolabelled antibodies is reversible bone marrow suppression. They produce response rates of 70%–90% in low-grade and follicular lymphoma and 40%–50% in transformed low-grade or intermediate-grade lymphomas. Both products produce higher response rates than related unlabelled antibodies, and both are highly active in patients who are relatively resistant to rituximab-based therapy. Median duration of response to a single course of treatment is about 1 year with complete remission rates that last 2 years or longer in about 25% of patients. Clinical trials suggest that anti- CD20 radioimmunotherapy is superior to total body irradiation in patients undergoing stem cell supported therapy for B-cell lymphoma, and that it is a safe and efficacious modality when used as consolidation therapy following chemotherapy. Among cytotoxic treatment options, current evidence suggests that one course of anti-CD20 radioimmunotherapy is as efficacious as six to eight cycles of combination chemotherapy. A major question that persists is how effective these agents are in the setting of rituximab- refractory lymphoma. These products have been underutilised because of the complexity of treatment coordination and concerns regarding reimbursement

Further Evidence for the Decay K+ to pi+ neutrino-antineutrino

Additional evidence for the rare kaon decay K+ to pi+ neutrino-antineutrino has been found in a new data set with comparable sensitivity to the previously reported result. One new event was observed in the pion momentum region examined, 211<P<229 MeV/c, bringing the total for the combined data set to two. Including all data taken, the backgrounds were estimated to contribute 0.15 pm 0.05 events. The branching ratio is B=1.57^{+1.75}_{-0.82} 10^{-10}.Comment: 10 pages, 2 figure

Measurement of Direct Photon Emission in K^+ -> pi^+ pi^0 gamma Decay

We have performed a measurement of the K^+ -> pi^+ pi^0 gamma decay and have observed 2 X 10^4 events. The best fit to the decay spectrum gives a branching ratio for direct photon emission of (4.7\pm0.8\pm0.3) X 10^{-6} in the pi^+ kinetic energy region of 55 to 90 MeV and requires no component due to interference with inner bremsstrahlung.Comment: 9 pages, 3 figures. To be submitted to PR

Search for the decay K+→π+ννˉK^+\to \pi^+ \nu \bar\nu in the momentum region Pπ<195 MeV/cP_\pi < 195 {\rm ~MeV/c}

We have searched for the decay $K^+ \to \pi^+ \nu \bar\nu$ in the kinematic region with pion momentum below the $K^+ \to \pi^+ \pi^0$ peak. One event was observed, consistent with the background estimate of $0.73\pm 0.18$. This implies an upper limit on $B(K^+ \to \pi^+ \nu \bar\nu)< 4.2\times 10^{-9}$ (90% C.L.), consistent with the recently measured branching ratio of $(1.57^{+1.75}_{-0.82}) \times 10^{-10}$, obtained using the standard model spectrum and the kinematic region above the $K^+ \to \pi^+ \pi^0$ peak. The same data were used to search for $K^+ \to \pi^+ X^0$, where $X^0$ is a weakly interacting neutral particle or system of particles with $150 < M_{X^0} < 250 {\rm ~MeV/c^2}$.Comment: 4 pages, 2 figure