Treatments

Treatments are broadly divided into the following five categories:

Chemotherapy
The most common course of non-Hodgkin’s chemotherapy is CHOP (cyclophosphamide, doxorubicin, prednisone, and vincristine), often with an addition of a monoclonal antibody, either rituximab (R-CHOP) or obinutuzumab (O-CHOP). Other non-Hodgkin’s chemotherapy regimens include a combination of bendamustine and rituximab, fludarabine, and R-CVP (rituximab, cyclophosphamide, prednisone, vincristine).² Chemotherapy is sometimes used to prepare the patient for a bone marrow transplant/stem cell transplant.³

Radiation therapy³
Non-Hodgkin’s radiation therapy utilizes high-energy beams such as X-rays or protons to destroy cancer cells. Radiation treatments for non-Hodgkin’s lymphoma can be used alone to destroy one or two targeted spots that contain cancerous lymphoma and can be used post-chemotherapy to destroy any lymphoma cells that remain.

Immunotherapy²
Non-Hodgkin’s immunotherapy treatments boost the patient’s own immune system to fight cancer. This includes the use of modified T cells and checkpoint inhibitors. In chimeric antigen receptor (CAR) T cell therapy (CAR T) some of the patient’s own T cells are removed and modified to contain specific proteins called receptors. The receptors allow these modified T cells to recognize cancer cells that have the target protein that binds to these receptors. These modified T cells are grown in a lab and then returned to the patient’s body.

Currently available FDA-approved CAR T non-Hodgkin’s immunotherapy options include axicabtagene ciloleucel, tisagenlecleucel, brexucabtagene autoleucel, and lisocabtagene maraleucel.

Immune checkpoint inhibitor: pembrolizumab

Targeted therapy²

• Anti-CD20 Monoclonal antibodies (mAbs): rituximab, obinutuzumab, and ofatumumab
• Anti-CD20 Radiolabeled antibodies: ibritumomab tiuxetan
• Antibody-drug conjugates (ADCs): brentuximab (CD30), loncastuximab tesirine-lpyl (CD19), polatuzumab vedotin-piiq (CD79b), tafasitamab-cxix (CD19)

Other targeted FDA-approved therapies for the treatment of NHL include:

• Bruton’s tyrosine kinase (BTK) inhibitors: ibrutinib, acalabrutinib, and zanubrutinib
• BCL-2 inhibitor: venetoclax
• PI3 kinase inhibitors: copanilisib, idelalisib, and duvelisib
• Selective inhibitor of nuclear export (SINE): selinexor
• Immunomodulatory drug: lenalidomide
• Enhancer of zeste homolog 2 (EZH2) inhibitor: tazemetostat
• Histone deacetylase (HDAC) inhibitors: belinostat, romidepsin, and vorinostat
• Proteasome inhibitor: and bortezomib¹

Bone Marrow Transplant^2,4
This involves using high doses of radiation and chemotherapy to suppress the patient’s bone marrow and immune system. Transplants are either autologous (patient’s own stem cells) or allogenic (donor stem cells).

Further details on each of these therapies can be accessed in the Resources section.

First-line Treatment
First-line treatment for most kinds of NHL is RCHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone). Other recommended regimens include dose-adjusted EPOCH (etoposide, prednisone, vincristine, cyclophosphamide, doxorubicin) + rituximab.

Diffuse large B-cell lymphoma
Figure 1 is an example of the treatment landscape for DLBCL. Similar information on treatments for each type of NHL can be explored in the CME activities section. Presenting symptoms include rapidly enlarging masses with both local and systemic symptoms (B symptoms with fever, night sweats, and weight loss).

Most patients with localized tumors can be cured with chemotherapy for non-Hodgkin’s alone or in combination with immunomodulatory agents. For advanced disease, more than half the patients are cured by doxorubicin-based combination therapy and rituximab.⁹