The FDA Approves Keytruda for Primary Mediastinal Large B-Cell Lymphoma (PMBCL)

Keytruda becomes the first anti-PD-1 therapy to be approved for PMBCL  

– This is the 2nd indication for Keytruda for a hematologic malignancy.

– The approval is based on tumor response rate and durability of response.

The FDA granted Merck (MRK) approval for its immuno-oncology checkpoint inhibitor Keytruda® for adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or for those who relapsed after two or more prior lines of therapy.

The approval is based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials.

Keytruda is not recommended for the treatment of patients with PMBCL who require urgent cytoreductive therapy. With this indication, Keytruda becomes the first anti-PD-1 therapy to be approved for the treatment of PMBCL, a type of non-Hodgkin lymphoma. This is the second indication for KEYTRUDA for the treatment of a hematologic malignancy.

Commenting on the approval, Philippe Armand, M.D., Ph.D., a medical oncologist in the Hematologic Oncology Treatment Center at Dana-Farber Cancer Institute said. “Relapsed or refractory PMBCL is often a challenging disease to treat, and many affected patients are young adults. In the clinical trial that supported this approval, treatment with Keytruda resulted in meaningful responses, including complete disease remission in some patients. This approval, therefore, provides another therapeutic option for patients with PMBCL who have progressed on or after prior therapies.”

Adverse Events

Immune-mediated reactions, including pneumonitis, colitis, hepatitis, endocrinopathies, nephritis, severe skin reactions and solid organ transplant rejection.

Based on the severity of the adverse reaction, Keytruda should be withheld or discontinued and corticosteroids administered if appropriate.

Immune-mediated complications, including fatal events, occurred in patients with classical Hodgkin lymphoma (cHL) who underwent allogeneic hematopoietic stem cell transplantation (HSCT) after treatment with Keytruda.

The instructions are to follow patients closely for early evidence of transplant-related complications and intervene promptly. In patients with a history of allogeneic HSCT, acute graft-versus-host disease (GVHD), including fatal GVHD following treatment with Keytruda, the oncologist should consider the benefit of the drug versus the risk of its adverse effects.  

To avoid Keytruda’s life-threatening infusion-related reactions, the recommendation is to monitor the patients for signs that point to an occurrence of the reactions

The drug should be stopped and permanently discontinued In case of grade 3 or 4 reactions occur.

Based on its mechanism of action, Keytruda can cause fetal harm when administered to a pregnant woman. Female patients of reproductive potential should be advised of the potential hazard to a fetus.

See the firm’s selected important safety information”.

Prohost Observations

 Merck has the industry’s largest immuno-oncology clinical research program, which involves more than 750 trials studying Keytruda across various cancers. The Keytruda clinical program seeks to understand the role of Keytruda across cancers and the factors that may predict a patient’s likelihood of benefitting from treatment with this checkpoint inhibitor immuno-oncology drug, including exploring several different biomarkers.

Keytruda has been already approved to treat a large number of different types and various organs’ cancers. No product has been granted such a large number of approvals.

It is important to note that checkpoint inhibitors, including Merck’s Ketyruda, Bristol-Myers’ (BMY) Obdivo have demonstrated efficacy on late-stage cancers that either have yet to find effective treatments, are refractory to effective treatments, or exhausted all conventional treatments. Although these immuno-oncology products are being approved and used in monotherapy and combination therapy for saving the lives of late-stage cancer patients, they have also been approved for first-line treatments in some cancers.

 Currently, Keytruda is approved for the following cancers:

– Unresectable or metastatic melanoma

First-line treatment of metastatic non-small cell lung cancer (NSCLC) in patients whose tumors have high PD-L1 expression with no EGFR or ALK genomic tumor aberrations.

Metastatic non-small-cell-lung cancer (NSCLC) in patients whose tumors express PD-L1 with disease progression on or after platinum-containing chemotherapy.

Metastatic non-squamous NSCLC. Combination of Keytruda + pemetrexed + carboplatin.

Recurrent or metastatic head and neck squamous cell carcinoma (HNSCC) with disease progression on or after platinum-containing chemotherapy.

Adult and pediatric patients with Classical Hodgkin refractory Lymphoma or who have relapsed after three or more prior lines of therapy.

 – Adult and pediatric primary mediastinal large B-cell lymphoma with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after 2 or more prior lines of therapy.

 Locally advanced or metastatic urothelial carcinoma in patients who are not eligible for cisplatin-containing chemotherapy.

Locally advanced or metastatic urothelial carcinoma in patients who have disease progression during or following platinum-containing chemotherapy or within 12 months of neoadjuvant or adjuvant treatment with platinum-containing chemotherapy.

– Adult and pediatric Microsatellite Instability-High (MSI-H) Cancer with unresectable or metastatic microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR)

Conclusion

The high number of approvals granted for Keytrudat enforced our conviction that  Merck is undervalued. We also believe the same for Bristol-Myers and other firms that have approved, or advanced investigational checkpoint inhibitors.

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