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The combination of carmustine, etoposide, cytarabine, and melphalan (BEAM) followed by autologous stem cell transplantation (ASCT) is a commonly used intensification regimen for patients with Hodgkin lymphoma. As etoposide and cytarabine dosing are not defined, we conducted a retrospective, multicenter study, to compare efficacy and toxicity in 130 patients with Hodgkin lymphoma receiving etoposide and cytarabine at either 200 mg/m 2 /d ( n  = 50), 400 mg/m 2 /d ( n  = 35), or etoposide 200 mg/m 2 /d and cytarabine 400 mg/m 2 /d ( n  = 45). Progression-free survival and overall survival were not associated with the intensity of conditioning. Increased conditioning intensity was associated with longer duration of thrombocytopenia, a higher number of transfused RBC and platelet units and a higher frequency of mucositis, but serious adverse events or infectious complications were not increased. The intensity of BEAM regimen was not associated with survival but with the rate of cytopenia and mucositis advocating for the use of lower dosing in frail patients.

Intratumoral injection of G100, a toll-like receptor 4 (TLR4) agonist, was shown pre-clinically to stimulate anti-tumor immune responses and tumor regression. This open-label, multicenter, phase 1/2 trial evaluated the safety, tolerability, and preliminary efficacy of intratumoral G100 injections following localized low-dose radiation in patients with follicular lymphoma (ClinicalTrials.gov #NCT02501473). The study was comprised of a G100 dose escalation (5 or 10 µg/dose, or 20 µg/dose for large tumors); a randomized component comparing G100 to G100 plus pembrolizumab; and G100 20 µg/dose expansion. Adverse events grade ≥3 were uncommon in patients treated with G100, and no unexpected toxicities were observed when combined with pembrolizumab. G100 20 µg ( n  = 18) resulted in an overall response rate of 33.3% and abscopal tumor regression in 72.2% of patients. This early-phase study provides a foundation for combining an intratumoral TLR4 agonist with agents to produce immune-mediated responses in follicular lymphoma with limited added toxicity.

Myeloproliferative neoplasms (MPN) are chronic disorders that can sometimes evolve into accelerated or leukemic phases. We retrospectively identified 122 patients with such blastic phases. The overall median survival was four months: 10.2 months for patients treated with intensive treatments compared to three months for best supportive care (p = .005). Azacytidine, intensive chemotherapies, or allogeneic stem cell transplantation gave the highest median survivals with 9, 10.2, and 19.4 months, respectively. Accelerated phases (AP) had a longer median survival compared to acute leukemia (4.8 months vs. 3.1 months; p = .02). In this retrospective and observational study, we observe that the longest survivals are seen in patients eligible for intensive treatments. Azacytidine shows interesting results in patients non-fit for intensive chemotherapy. Supportive care should probably be restricted to elderly patients and those with unfavorable karyotype. An early diagnosis of AP could also result in a better survival rate.

Obinutuzumab (OBZ) shows stronger antibody-dependent cell cytotoxicity (ADCC) compared to rituximab and improved clinical activity for treating certain CD20 + neoplasia. However, the efficacy of monoclonal antibody (mAb) as a monotherapy is limited. Natural Killer (NK) cells are mediators of ADCC. Hematological cancer patients possess antitumor NK cells that are unable to control disease, possibly because they are dysfunctional. The immunomodulatory drug lenalidomide (LEN) could be a treatment to restore exhausted NK cell cytotoxic functions. The clinical trial GALEN is a Phase Ib/II study of OBZ combined with LEN for the treatment of relapsed/refractory follicular and aggressive (DLBCL and MCL) B-cell Lymphoma. During treatment, we analyzed specific aspects of NK cell biology. Treatment reversed the immature NK phenotype of patients and increased expression of NK activating receptors. Inhibitory receptors were either unchanged or decreased. There was a strong NK response at the end of the 1st cycle: NK number and intracellular granzyme B (GrzB) expression decreased, degranulation increased and NK responded better to allogeneic target challenge. Moreover, the interaction of NK cells with B cell targets, measured by trogocytosis, decreased during treatment. At the end of treatment, when target cells had been wiped out, the proportion of reactive NK cells (CD69 + , CD45RARO + , CD107a + , CD19 + ) strongly decreased. Because all patients received LEN and OBZ, it was uncertain which drug was responsible of our observations, or even if a combination of both products was necessary for the described effects on this lymphocyte lineage.

In November 2015, the CALYM Carnot Institute held a 2-d workshop to discuss the current and future development of immunomodulatory antibodies for the treatment of lymphoma. Highlights from the workshop are presented in this article.

Some evidence suggests that monoclonal antibodies (mAb) can induce an adaptive immune response against tumor cells ("vaccinal effect"). Recently, we have shown that an anti-CD137 mAb can enhance the "vaccinal effect" of an anti-tumor mAb (cetuximab), thereby transforming a passive, monoclonal, short-term immunotherapy into an active, polyclonal, long-lasting immune response.

Monoclonal antibodies (mAb) induce tumor regression through antibody-dependant cellular cytotoxicity (ADCC). We recently showed that an agonistic anti-CD137 mAb stimulates natural killer (NK) cells which have been activated by a tumor-specific mAb, resulting in increased ADCC against cancer cells.

Data on all patients diagnosed with Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL) aged 55 or older, seen in our institution over a 17-year period, were studied to determine the incidence and range of clinical and biological subtypes, and the outcome of different therapeutic approaches. Twenty-five Ph+ ALL cases (median age: 64 years) were diagnosed between 1986 and 2003 (28% of all B-lineage elderly ALL seen during this period). Karyotypic analysis was performed successfully in 22 cases, while 3 were only diagnosed by molecular biology analysis. All patients had B-cell lineage ALL. Co-expression of myeloid markers was observed in 20% of tested cases. One patient died before chemotherapy could be given. All other patients received "curative" treatment according to different protocols used during the period of study. Overall the complete remission (CR) rate was 76% (95% confidence interval, CI: 55-91%). Fifteen patients achieved CR after one course of chemotherapy and 4 patients after salvage therapy. Median disease-free survival (DFS) of the entire cohort was 5.6 months (95% CI: 4.5-8.4 months) and median overall survival was 10.1 months (95% CI: 7.9-13 months). In multivariate analysis, age>or=70 years was of poor prognostic value for achieving CR (p=0.05) and hyperleukocytosis at diagnosis was of poor prognostic value for overall survival (p=0.001). Overall survival duration was not significantly influenced by achieving CR. Ph+ ALL patients did not show a significant difference in terms of outcome as compared with Philadelphia-negative ALL patients. The very poor overall outcome in elderly patients with Ph+ ALL may be significantly improved by the introduction of imatinib mesylate into current treatment regimens.