B-Cell Lymphoma Refractory: Understanding and Treatment Options

When lymphoma does not respond well to treatment or returns after a period of improvement, patients face a challenging situation that requires specialized care and new treatment approaches.

Table of contents

• What Is Relapsed and Refractory B-Cell Lymphoma
• How Common Is This Condition
• Treatment Options
• Stem Cell Transplantation
• CAR T-Cell Therapy
• Chemotherapy Regimens
• Other Treatment Approaches

What Is Relapsed and Refractory B-Cell Lymphoma

The term relapsed refers to disease that reappears or grows again after a period of remission, which means a time when the signs and symptoms of the disease are reduced or gone^[1]. This cancer can come back in the original location or in other parts of the body^[10].

The term refractory is used to describe when the lymphoma does not respond to treatment, meaning that the cancer cells continue to grow, or when the response to treatment does not last very long^[1]. Refractory lymphoma is different from relapsed lymphoma because the signs and symptoms do not improve much or at all^[10].

How Common Is This Condition

Overall, around 40% of patients with diffuse large B-cell lymphoma (DLBCL), a common type of B-cell lymphoma, have refractory disease or relapse after the first line of treatment^[2]. Specifically, about 15 to 20% of patients have refractory disease, while 20 to 30% experience relapse^[2].

Until relatively recently, the prognosis of patients with relapsed or refractory disease was very poor and treatment options were very limited^[2]. In recent years, several novel therapies have been approved that provide more effective options than conventional chemotherapy^[2].

Treatment Options

Treatment remains challenging for patients whose disease returns or does not respond to initial therapy, and outcomes are often poor given the aggressive nature of this disease^[5]. However, multiple treatment options have become available in recent years that have broadened the treatment landscape^[5].

Your healthcare team will review your previous treatments to try to figure out what worked, what did not work, and why. That information can guide the next steps, whether that means modifying existing treatments or trying new options^[10]. Treatment is tailored individually to each person’s situation^[10].

Stem Cell Transplantation

High-dose chemotherapy followed by stem cell transplantation can be used to treat patients with disease that is refractory or relapsed following initial chemotherapy^[1]. The majority of patients undergoing stem cell transplantation will have an autologous transplant, which means the patient receives his or her own stem cells that were collected prior to the procedure^[1]. Occasionally, a patient will undergo an allogeneic transplant, where the patient receives stem cells from a donor^[1].

This treatment replaces damaged stem cells with healthy ones that can make new blood cells^[10].

CAR T-Cell Therapy

For some patients with relapsed or refractory disease, a form of immunotherapy called chimeric antigen receptor (CAR) T-cell therapy may be a possible treatment option^[1]. CAR T-cell therapy has become the new standard treatment for patients with refractory or early relapsed disease^[2].

This therapy works by engineering a patient’s T-cells, which are a type of immune cell, to target and kill lymphoma cells^[10]. The approved CAR T-cell therapies include^[1]:

• axicabtagene ciloleucel (Yescarta)
• Lisocabtagene Maraleucel (liso-cel, Breyanzi)
• tisagenlecleucel (Kymriah)

Chemotherapy Regimens

For patients with relapsed or refractory disease, combination chemotherapy regimens are available. These second-line regimens include^[1]:

• ifosfamide, carboplatin, and etoposide (ICE)
• dexamethasone, cisplatin, and cytarabine (DHAP)
• gemcitabine-based therapy
• bendamustine (Treanda) plus rituximab (Rituxan)
• lenalidomide (Revlimid) plus rituximab (Rituxan)

Combinations of chemotherapy drugs could be effective in treating this condition^[10].

Other Treatment Approaches

Several other approved treatment options are available for patients with relapsed or refractory disease^[1]:

• polatuzumab vedotin-piiq (Polivy)
• selinexor (Xpovio)
• tafasitamab-cxix (Monjuvi)
• epcoritamab-bysp (Epkinly)
• glofitamab-gxbm (Columvi)

Targeted therapies are drugs like ibrutinib or venetoclax that focus on specific molecules or pathways involved in cancer growth. These treatments may help keep cancer cells from multiplying without much damage to normal cells^[10].

Immunotherapies, such as checkpoint inhibitors, monoclonal antibodies, or bispecific therapies, may help the immune system recognize and destroy cancer cells^[10].

For patients who have a subset of disease called primary mediastinal large B-cell lymphoma (PMBCL), pembrolizumab (Keytruda) is available as a second-line treatment option^[1].

In some cases, radiation therapy may be an option for treating these cancers^[10]. You may also want to participate in clinical trials, which can give you access to cutting-edge therapies, new treatment approaches, and opportunities for better outcomes^[10].