Updates on the latest immunotherapeutic options

The field of immunotherapy has been rapidly evolving and is increasingly utilized in the management of lymphomas.1 Currently, various immunotherapeutic modalities have been pursued including monoclonal antibodies, bispecific T-cell engagers (BiTEs), checkpoint inhibitors and chimeric antigen receptor T-cell (CAR-T) therapies.1

For monoclonal antibodies, Prof. Kwong, Yok-Lam commented that obinutuzumab is vastly under-utilized in both the private and public setting. When managing chronic lymphocytic leukemia (CLL), obinutuzumab plus chlorambucil (G-Chl) had a superior progression-free survival (PFS) than rituximab-chlorambucil (26.7 vs. 15.2 months; HR=0.39; 95% CI: 0.31-0.49; p<0.001), with venetoclax-obinutuzumab demonstrating an even greater PFS benefit than G-Chl (HR=0.33; 95% CI: 0.22-0.51; p<0.001).2,3 When managing follicular lymphoma (FL), obinutuzumabbased chemotherapy also had a significantly lower risk of progression, relapse or death than rituximab-based chemotherapy (HR=0.66; 95% CI: 0.51-0.85; p=0.001).4 Based on these studies, Prof. Kwong concluded that, “In low-grade B-cell lymphoma, there is a distinct advantage of using obinutuzumab over rituximab.”

For BiTEs, blinatumomab has significantly improved overall survival (OS) over chemotherapy when treating Philadelphia chromosome (Ph)- negative acute lymphoblastic leukemia (ALL) patients (7.7 vs. 4.0 months, HR=0.71; 95% CI: 0.55-0.93; p=0.01).5 In the Ph-positive ALL setting, blinatumomab also showed a similar OS of 7.1 months, with patients achieving minimal residual disease complete response (MRD CR) at cycle 1 attaining greater survival benefit over MRD non-responders (HR=2.63; 95% CI: 1.40-4.96; p=0.002).6,7 Importantly, an induction therapy with dasatinib before blinatumomab resulted in a high molecular response of 60%, with a 18-month OS and disease-free survival of 95% and 88%, respectively.8 Considering the survival benefit of tyrosine kinase inhibitors (TKIs) plus BiTEs , Prof. Kwong summarized that, “There is a possibility in the long run that some patients with Ph-positive ALL may be cured using a combination of TKI and BiTE.”

For checkpoint inhibitors, Prof. Kwong believed that while immune checkpoint blockade is applicable to most lymphoma patients, not all clinicians could identify and properly manage the early signs of immune-related adverse events (irAEs).9 Psoriasiform dermatitis is an irAE that often not fully recognized. Punctate vitiligo is another common irAE, and may be a harbinger of generalized vitiligo. Pneumonitis due to anti-PD1 treatment must be distinguished from infection, as antibiotics would be ineffective, and corticosteroids or mycophenolate mofetil should be administered. Patients may also develop endocrine disorders including adrenalitis, hypothyroidism and hypophysitis when receiving anti-PD-1 therapy. To better prevent these irAEs, Prof. Kwong recommended constant monitoring of thyroid function and cortisol level with routine chest X-ray performed.

When considering CAR-T therapy, Prof. Kwong noted that tisagenlecleucel had achieved a 6-month event-free survival and OS of 73% and 90%, respectively, in patients with relapsed/refractory ALL.10 While not a cure for every patient, tisagenlecleucel achieved an overall remission rate of 81% within 3 months, with most of these ALL patients achieving durable remission.10 For patients with relapsed/ refractory diffuse large B-cell lymphoma (DLBCL), tisagenlecleucel achieved CR in 40% of patients with a relapse-free survival (RFS) of 79% among those with CR.11

Although multiple immunotherapeutic options are now available for the treatment of hematologic malignancies, not one specific therapy is necessarily superior to another, with the optimal choice dependent on the patients and clinical settings. To better optimize immunotherapy, Prof. Kwong recommended clinicians to familiarize themselves with the different treatment modalities so that the treatment sequence can be better determined. “The sequencing of immunotherapy choices is important, and these advanced therapies ought to be performed in centres with experience in each modality,” concluded Prof. Kwong.

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