Razan Mohty, Hematology/Oncology fellow at the American University of Beirut Medical Center, and one of the EBMT's 2018 Young Ambassadors, attended the 60th ASH Annual Meeting that took place in San Diego from December 1-4. Razan gives us her perspectives.
The American Society of Hematology Meeting this year brought lots of new data and results. Loads of abstracts were presented tackling all the new innovations and updates in the field of Hematology.
Leukemias were the subjects of many presentations, in particular acute myeloid leukemia (AML). Despite therapeutic advances, the outcome of patients with AML is suboptimal especially in high risk population. Since 1970, cytotoxic chemotherapy is the backbone of the treatment of AML. However, with genomic and molecular understanding of AML numerous druggable targets were identified moving forward the treatment of AML. Major data targeted therapies were presented including BCL2 inhibitors (Venetoclax), FLT3 inhibitors, with induction, as salvage or maintenance therapy, and IDH 1/2 inhibitors, moving to the upfront therapy. In a phase Ib trial presented by Dr Pollyea, Venetoclax with hypomethylating agents showed high rates of deep and durable response with good safety profile as upfront therapy in older patients ineligible for induction chemotherapy. Dr Stein presented a phase I study on Ivosidenib and Enasidenib combined with induction and consolidation chemotherapy for newly diagnosed IDH1/2 mutated AML showing promising results in term of high remission rates, MRD negativity and safety profile. Nevertheless, Dr Cortes presented data from a phase III, Quantum-R, trial showing survival benefit with the use of single agent Quizertinib, a potent FLT3-ITD inhibitor, over chemotherapy in relapsed/refractory (R/R) AML. In the post-transplant setting, the use of Sorafenib significantly improves overall survival as shown in a retrospective study presented by Dr Bazarbachi. In addition, Aurora A kinase inhibitor, Alisertib, which regulation of mitotic progression, showed good results with MRD negativity when used in combination with induction chemotherapy in high risk patient.
Beside targeted therapy, immunotherapy became a major player in the treatment of AML. Lots of data were presented on antibody-drug conjugate (ADC), bispecific antibodies (BiTes) and immune checkpoint inhibitors. Dr Cortes in IMGN779 trial of CD33-targeting ADC showed some response with good tolerability in R/R AML. In addition, a phase I study of Brentuximab (BV) combined with reinduction chemotherapy in patients with CD30+ R/R AML showed well tolerability with good response rate. Dr Ravandi presented a first in human phase I trial of AMG-330, a CD33/CD3 BiTes in R/R AML which showed evidence of tolerability with good responses. Regarding immune checkpoints, many data were presented and it is too early to talk about responses. Among all abstracts on CAR-T cells in AML, THINK trial, a phase I trial on NKG2D where cells were infused without conditioning therapy reported acceptable rate of cytokine release syndrome (CRS) and good responses.
In acute lymphoblastic leukemia (ALL), numerous data were presented, mainly tackling ADC and BiTes. Dr Sasaki presented results of 2 phase II trials showing efficacy and safety of Inotuzumab Ozogamicin with or without Blinatumomab with low-intensity chemotherapy for the treatment of R/R and newly diagnosed Philadelphia-chromosome negative (Ph-) ALL. Dr Advani presented data of the phase II trial, SWOG 1318 of upfront blinatumomab followed by maintenance POMP in older patient newly diagnosed Ph- B-ALL. Results are promising with a good overall response rate with deep responses and MRD negativity and an acceptable safety profile.
In multiple myeloma (MM), many exciting therapeutic novelties were presented including monoclonal antibodies, moving to the upfront setting, BiTes and most importantly CAR-T cells. These therapeutic waves may render myeloma a curative disease rather than a chronic one. Nevertheless, we are learning more and more how to combine these treatments to achieve a better cure rate with a negative MRD at the lowest detection level. One of the most important studies is the MAIA trial presented by Dr Facon showing the efficacy and safety of Daratumumab (D) combined with Revlimid (R) and Dexamethasone (d) versus Rd alone in transplant ineligible newly diagnosed MM. In addition, Tourmaline-MM3 phase III trial showed improved PFS, conversion to MRD negativity and excellent safety profile with oral proteasome inhibitor–based maintenance, Ixasomib (I) for patients with newly diagnosed MM who receive auto-transplant. Other phase II trials reported efficacy and safety of different combinations in newly diagnosed MM: D plus IRd, an all oral regimen, the HOVON 143 trial combining IDd in unfit and frail patients, the GRIFFIN trial combining D-VRD. In the setting of pentarefractory MM, the use of oral Selinexor, a XPO1 inhibitor, with low dose dexamethasone show deep and durable reponse with better tolerability. Nevertheless, Venetoclax came to the world of MM alone or in combination with MCL1 inhibitor, especially in patients with t(11;14). BiTes were also used in MM: AMG420, an anti-BCMA, induce MRD negativity in R/R MM. Regarding CAR-T cells, BCMA seems to be the best target in MM. Among all 6 trials, impressive results of the LCAR-B38M confirmed high response rate, high degree of MRD negativity, very good tolerability with low CRS rate with low cell dose used compared to other trials. The P-BCMA 101 trial showed efficacy in controlling the disease and decreasing tumor burden in R/R MM without neurotoxicity. Other CAR-T cells include the bb21217, and the Chinese CART cells in combination with autotransplant consolidate therapy in high risk MM. moving CART cells to the frontline setting.
In chronic lymphocytic leukemia, a practice changing trial proved the superiority of Ibrutinib with Rituximab over the standard of care chemoimmunotherapy Fludarabine, cyclophosphamide and Rituximab. In Peripheral T-cell lymphoma, ECHELON-2, a phase III trial comparing BV plus CHP to CHOP the standard of care in patients with CD30+ T-cell lymphoma showed better PFS and OS in the BV arm with same toxicity. Another trial, the AUGMENT phase III trial lenalidomide + rituximab vs rituximab + Placebo in indolent non-Hodgkin lymphoma showed better PFS and higher but manageable toxicities.
In term of GvHD, a serious complication after allo-transplant, until now there is no treatment for steroids refractory (SR) GvHD. Among the most important studies on SR GvHD, Dr Jagasia presented promising results of a phase II trial, REACH1, evaluating Ruxolutinib plus corticosteroids for the treatment of SR GvHD with very good response rate. Another important study on SR GvHD is the Odyssee study by Dr Mohty, a phase I/II multicenter trial on the use of autologous fecal microbiota transfer (FMT) for the prevention of dysbiosis complications showing interesting results with high response rates.
In summary, a lot of hope exist for our patients. The field of hematology is moving rapidly. Immunotherapy and cellular therapy started to dominate. I am enthusiastic about the data on combination of immune and cellular therapy next year. #ASH18 was an exciting meeting in the beautiful city of San Diego. See you all in Orlando next year #ASH19.
