Professor Nathan Fowler presented the current state of play with FL chemotherapy-free treatments. He 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) of which, however, little is known of the 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 it is associated with toxicity, such as infections, fatigue, nausea, cytopenias, 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, stating that they (copanlisib [our interview with Prof Kim can be viewed
here], duvelisib [our review of the DYNAMO trial can be found
here], idelalisib [link to interview with Dr Sellner
here, and our review of the work
here], umbralisib and INCB050465) are similar in terms of ORR (40-60%) and a median PFS at around 11 months. However, they differ slightly in their side effect profile. All PI3K inhibitors appear to induce neutropenia, diarrhea, nausea, fatigue, and coughing at varying degrees. In addition, copanlisib seems to cause hypertension and was related to deaths from respiratory failure and circulatory relapse, while idelalisib, umbralisib, and INCB050465 may also cause transaminitis in some patients.
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 a similar efficacy as chemotherapy, but with different side effects (cutaneous reactions and rashes with R2, more febrile neutropenia with chemotherapy). The AUGMENT trial (we summarised the publication
here) assessed R2 as a treatment in cases of R/R FL and found it to convey better ORR and PFS rates also in high-risk patients when compared to rituximab alone, yet had higher toxicity. In answer to questions, 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. Prof. Fowler brought his presentation to a close with some preliminary data on tazemetostat (an EZH2 inhibitor; please see Dr. Salles interview on tazemetostat for R/R FL
here) and CTL109, a CAR T-cell product.
Mantle cell lymphoma (MCL)