Lymphoma Hub Satellite Symposium 2019 | Chemo-free approaches for the treatment of lymphoid malignancies -  Professor Nathan Fowler

The Lymphoma Hub Satellite Symposium at 15-ICML brought together an international panel of experts to discuss the novel chemotherapy-free treatment approaches for lymphoid malignancies. Professor Nathan Fowler, University of Texas MD Anderson Cancer Centre, Houston, US, presented the current state of play with FL chemotherapy-free treatments.

Professor Fowler demonstrated that long-term survival rates have more than doubled in the last 50 years with improvements in chemotherapy regimens and the addition of rituximab. He also highlighted the influx of newer treatments in recent years (such as antibodies, PI3K inhibitors, and immunomodulatory treatments) with little known long-term outcomes.

Prof. Fowler went on to discuss the distinctive tumor microenvironment and related immune dysfunction associated with FL which contribute to the promotion of tumor cell survival and proliferation. Therapeutics such as rituximab and lenalidomide can be used to exploit these altered mechanisms. Although many patients benefit from chemotherapy, the treatment is associated with side effects, including fatigue, nausea, cytopenia, and even secondary malignancies. As many patients are not cured, Prof. Fowler emphasized the need for alternative chemotherapy-free treatment regimens.

He went on to discuss PI3K inhibitors, the similarity in terms of ORR (40-60%) and median PFS at around 11 months, and slight differences in their toxicity profile. All PI3K inhibitors appear to induce neutropenia, diarrhea, nausea, fatigue, and coughing at varying degrees. He then discussed the R2 combination treatment (lenalidomide and rituximab) presenting the RELEVANCE and AUGMENT trial data.

The RELEVANCE trial assessed R2 as a front-line treatment and demonstrated similar efficacy to chemotherapy, but with different side effects (cutaneous reactions and rashes with R2, more febrile neutropenia with chemotherapy). The AUGMENT trial assessed R2 as a treatment in R/R FL and found it to convey better ORR and PFS rates also in high-risk patients when compared to rituximab alone, yet with higher toxicity.

Prof. Fowler said he would treat most patients with R2 unless there were signs of transformation. In terms of post-treatment transformation, he had seen very few R2 treated patients with transformation at 5 years follow up. He brought his presentation to a close with some preliminary data on tazemetostat and CTL109, a CAR T-cell product.