1.Antibodies to watch in 2016.
Reichert JM1. MAbs. 2016 Feb-Mar;8(2):197-204. doi: 10.1080/19420862.2015.1125583. Epub 2015 Dec 14.
The number of novel antibody therapeutics that received first marketing approvals in 2015 met expectations, with 6 (alirocumab (Praluent®), evolocumab (Repatha®), daratumumab (Darzalex®), dinutuximab (Unituxin®), idarucizumab (Praxbind®), mepolizumab (Nucala®)) granted first approvals as of mid-November*. Seven novel antibody therapeutics (begelomab, brodalumab, elotuzumab, ixekizumab, necitumumab, obiltoxaximab, reslizumab) are in regulatory review, and thus a similar number, if not more, are projected to gain first approvals in 2016. Commercial late-stage antibody therapeutics development exceeded expectations by increasing from 39 candidates in Phase 3 studies as of late 2014 to 53 as of late 2015. Of the 53 candidates, transitions to regulatory review by the end of 2016 are projected for 8 (atezolizumab, benralizumab, bimagrumab, durvalumab, inotuzumab ozogamicin, lebrikizumab, ocrelizumab, tremelimumab). Other "antibodies to watch" include 15 candidates (bavituximab, bococizumab, dupilumab, fasinumab, fulranumab, gevokizumab, guselkumab, ibalizumab, LY2951742, onartuzumab, REGN2222, roledumab, romosozumab, sirukumab, Xilonix) undergoing evaluation in Phase 3 studies that have estimated primary completion dates in 2016.
2.Inotuzumab ozogamicin in the treatment of acute lymphoblastic leukemia.
Dahl J1, Marx K1, Jabbour E1. Expert Rev Hematol. 2016 Apr;9(4):329-34. doi: 10.1586/17474086.2016.1143771. Epub 2016 Mar 22.
Over 90% of leukemic blasts in patients with acute lymphoblastic leukemia express the marker CD22. Inotuzumab ozogamicin (INO) is a CD22-directed humanized monoclonal antibody conjugated to the potent cytotoxin, calicheamicin, via an acid labile linker. INO has shown high rates of response in the treatment of relapsed and refractory (R/R) ALL in single-agent studies, with fewer adverse effects than traditional cytotoxic chemotherapy. Given this experience, studies are now being done to evaluate INO in combination with low-intensity chemotherapy as frontline treatment for older adults with ALL and patients with R/R disease. Herein we will discuss the use of INO in the treatment of acute lymphoblastic leukemia.
3.Role of inotuzumab ozogamicin in the treatment of relapsed/refractory acute lymphoblastic leukemia.
George B1, Kantarjian H1, Jabbour E1, Jain N1. Immunotherapy. 2016 Feb;8(2):135-43. doi: 10.2217/imt.15.108. Epub 2016 Jan 18.
Inotuzumab ozogamicin is a humanized anti-CD22 monoclonal antibody bound to a toxic natural calicheamicin, which is under investigation for the treatment of relapsed/refractory acute lymphoblastic leukemia. CD22 is commonly expressed in 90-100% of malignant mature B-lymphocyte lineage. The first Phase II study with inotuzumab ozogamicin conducted by Kantarjian et al. gave the opportunity for heavily pretreated patients with acute lymphoblastic leukemia to go for allogeneic stem cell transplant. Inotuzumab is well-tolerated with the exception of veno-occlusive disease. Overall inotuzumab ozogamicin is potentially an encouraging and promising therapy for patients.
4.Immunotherapy approaches to treat adult acute lymphoblastic leukemia.
Maino E1, Bonifacio M2, Scattolin AM1, Bassan R1. Expert Rev Hematol. 2016 Apr 8:1-15. [Epub ahead of print]
Recent developments in immunotherapy are improving treatment results of B-precursor acute lymphoblastic leukemia. This advancement is promoted by new monoclonal antibodies such as inotuzumab ozogamicin, ofatumumab and blinatumomab, by rituximab, and by genetically engineered chimeric antigen receptor-modified T-cells. These treatments, variously targeting CD22, CD20 and CD19 antigens, yield unprecedented high rates of hematologic and molecular remissions even when used in monotherapy and in chemo-resistant or post-transplantation relapsed patients. Beside the encouraging results in relapsed/refractory disease, these agents may open a totally new era in the frontline management of this illness, redefining treatment standards and options for different risk subsets and placing the achievement of a molecular remission at the forefront of treatment objectives. The ever increasing importance of modern immunotherapy in improving treatment design and therapeutic outcome is reviewed.