Mantle Cell Lymphoma Recurrent

Mantle cell lymphoma typically follows a pattern of remission and relapse, where the disease responds well to initial treatment but tends to return over time. Each time the cancer comes back, treatment options remain available, though responses often become shorter with each subsequent relapse.

Table of contents

• Understanding Relapsed and Refractory Mantle Cell Lymphoma
• Patterns of Survival with Recurrent Disease
• Factors That Guide Treatment Decisions
• Treatment Options for Relapsed Disease
• Stem Cell Transplant Options

Understanding Relapsed and Refractory Mantle Cell Lymphoma

Although mantle cell lymphoma usually responds well to initial treatment, patients do tend to experience the disease returning^[1]. The term relapsed refers to disease that reappears or grows again after a period of remission, which is when you no longer have signs of cancer^[1][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].

With mantle cell lymphoma, you might have periods of remission followed by periods of recurrence. That means the cancer can go away and come back, often several times^[2]. Most patients with mantle cell lymphoma have stage III or IV disease at diagnosis. Like low-grade lymphomas, mantle cell lymphoma is highly responsive to treatment, but not curable in most cases^[4].

Disease relapse is almost universal, and most patients require multiple lines of treatment in their lifetime^[6]. If your cancer comes back more than once, you might need a different treatment each time^[10].

Patterns of Survival with Recurrent Disease

Research shows that survival and response times tend to shorten with each relapse. After second-line therapy, the median overall survival and progression-free survival were 41.1 months and 14.0 months respectively. After third-line treatment, these decreased to 25.2 months and 6.5 months. Following fourth-line therapy, the median overall survival was 14.4 months and progression-free survival was 5.0 months^[6].

It is generally understood in mantle cell lymphoma that the remission duration is the longest after frontline therapy and successively shortens with subsequent lines of therapy^[6]. Early treatment failure after first-line regimens was associated with worse overall survival compared to later relapses^[6].

Approximately a third of patients treated with certain targeted therapies are refractory, and up to 69% of patients who do respond at first will experience disease progression by two years on treatment^[9].

Factors That Guide Treatment Decisions

For patients who relapse or become refractory, secondary therapies may be successful in providing another remission^[1]. Like other forms of non-Hodgkin lymphomas, there is no consensus on the best treatment for relapsed or refractory mantle cell lymphoma. However, there are an increasing number of treatment options available for these patients^[1].

The type of treatment recommended for any individual patient depends on several factors, including the timing of the relapse, the patient’s age, extent of disease, overall health, and prior therapies received^[1][10]. Your doctor will choose a drug or combination of medications based on things like your age, overall health, how long you were in remission, and which treatments you’ve already tried and how well they worked^[10].

You may get the same treatment you had before if it was helpful^[10].

Treatment Options for Relapsed Disease

Several agents have been approved by the FDA for treatment of relapsed or refractory mantle cell lymphoma^[1]:

• Acalabrutinib (Calquence)
• Bortezomib (Velcade) with or without rituximab
• Brexucabtagene Autoleucel (Tecartus)
• Lenalidomide (Revlimid) with or without rituximab
• Zanubrutinib (Brukinsa)
• Pirtobrutinib (Jaypirca)^[10]

Although not approved in combination, bortezomib and lenalidomide may be used with rituximab (Rituxan)^[1].

Targeted drugs focus on specific substances in your body that help your cancer grow. Acalabrutinib, ibrutinib, pirtobrutinib, and zanubrutinib are medicines called BTK inhibitors because they block the protein Bruton’s tyrosine kinase, which mantle cell cancer cells need to grow^[10]. These medicines come as pills that you take once or twice a day^[10].

BTK inhibitors can cause side effects. The most common ones are low blood cell counts, headache, diarrhea, tiredness, bruises, and muscle pain. Other possible problems include excess bleeding, infections, abnormal heart rhythms, and another cancer, such as skin cancer^[10].

Lenalidomide (Revlimid) is a drug that acts on your immune system—your body’s defense against germs—to kill cancer cells. It ramps up your immune system to attack the cancer, stops new cancer cells from growing, and blocks the growth of blood vessels that feed the cancer^[10]. You could get this drug if you’ve tried at least two other treatments and one of them was the chemotherapy drug bortezomib (Velcade)^[10].

Rituximab (Rituxan) is a type of drug called a monoclonal antibody. It works with your immune system to kill cancer cells. You may get rituximab together with chemotherapy. Doctors call this combination chemo-immunotherapy^[10].

Additional agents and regimens that are commonly used for the treatment of relapsed/refractory mantle cell lymphoma include^[1]:

• Bendamustine (Treanda) with or without rituximab
• Combination chemotherapy with or without rituximab

Contemporary consensus is to preferentially offer chimeric antigen receptor (CAR) T-cell therapy for appropriate patients^[9]. This represents a significant development in the treatment of recurrent mantle cell lymphoma^[8].

Stem Cell Transplant Options

Stem cell transplant can be effective in patients with relapsed or refractory mantle cell lymphoma. There are two types of stem cell transplants: allogeneic, in which patients receive stem cells from another person, and autologous, in which patients receive their own stem cells^[1].

Autologous stem cell transplant is generally considered after initial therapy rather than in relapse, but may be an option for medically fit patients who have shown a good response to treatment of their relapsed mantle cell lymphoma^[1].

In the case of younger, medically fit patients, intensive chemotherapy followed by allogeneic stem cell transplantation is a higher risk, but potentially a curative option^[1]. Allogeneic stem cell transplant has an established role in appropriate candidates^[9].