relapsed/refractory diffuse large B-cell lymphoma

Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Relapsed/refractory DLBCL is a type of non-Hodgkin lymphoma that does not respond to initial treatment or recurs after treatment. This condition accounts for approximately one-third of patients with DLBCL and remains a major cause of morbidity and mortality [2].

Characteristics

• Relapsed DLBCL refers to the recurrence of cancer cells after initial treatment.
• Refractory DLBCL refers to the failure of cancer cells to respond to initial treatment, resulting in continued growth and progression of the disease.

Prevalence

Approximately 30% to 40% of patients will develop relapsed/refractory DLBCL, leading to significant morbidity and mortality [7].

Treatment Landscape

The current treatment landscape for relapsed/refractory DLBCL is evolving, with various options available, including salvage chemotherapy, immunotherapy, and targeted therapies. Key opinion leaders share a broad perspective on the current treatment landscape [5].

Definitions

• The most narrow definition of refractory DLBCL is failure to achieve a partial or complete response (CR) to first-line treatment.
• Another common definition includes stable disease (SD) or progressive disease (PD) as the best response to first- or later-line treatment [4][6].

References:

[1] Not applicable

[2] by LS Raut · 2014 · Cited by 112 — Relapsed-Refractory Diffuse Large B Cell Lymphoma (RR DLBCL)

[3] Not applicable

[4] Jun 26, 2024 — The most narrow definition is failure to achieve a partial6,7 or complete response (CR) to 1L treatment.

[5] Jun 19, 2023 — Key opinion leaders share a broad perspective on relapsed/refractory diffuse large B-cell lymphoma and the current treatment landscape.

[6] by ERA Pennings · 2024 · Cited by 6 — In SCHOLAR-1 refractory DLBCL was defined as stable disease (SD) or progressive disease (PD) as the best response to first- or later-line treatment.

[7] Jun 16, 2022 — Approximately 30% to 40% of patients will develop relapsed/refractory (R/R) DLBCL, leading to significant morbidity and mortality.

Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) can exhibit a range of signs and symptoms, which may vary from person to person. Here are some common indicators:

• Swollen or enlarged lymph nodes: One of the most noticeable signs is having swollen or enlarged lymph nodes, which can be felt underneath your skin and are often painless [1].
• B symptoms: Around 1 in 3 people with DLBCL experience fevers, night sweats, and unexplained weight loss, known as 'B symptoms' [3]. These symptoms can also include fatigue and loss of appetite.
• Other symptoms: In some cases, relapsed or refractory DLBCL may present with additional symptoms such as nausea, vomiting, diarrhea, lack of appetite, lethargy, blood in the urine, heart problems, seizures, muscle cramps, and more [5].

It's essential to note that not everyone will experience all of these symptoms, and their severity can vary. If you're experiencing any of these signs or symptoms, it's crucial to consult with your healthcare provider for proper evaluation and treatment.

References: [1] Context result 1 [3] Context result 3 [5] Context result 5

Diagnostic Tests for Relapsed/Refractory Diffuse Large B-Cell Lymphoma (DLBCL)

Relapsed or refractory DLBCL requires a thorough diagnostic evaluation to confirm the diagnosis and assess the extent of disease. The following tests are commonly used:

• Biopsy: A biopsy is the gold standard for diagnosing DLBCL. It involves removing a sample of tissue from an affected lymph node, which is then examined under a microscope by a specialist (citations [4], [9], [10]). This test can confirm the presence of cancer cells and help determine the type of lymphoma.
• Imaging studies: Imaging tests such as computed tomography (CT) scans are used to assess the extent of disease and identify any potential complications (citations [2], [3]). CT scans can also be used to monitor the response to treatment.
• Blood tests: Complete blood cell count with differential, comprehensive metabolic panel, and other blood tests may be ordered to evaluate the patient's overall health and detect any potential complications (citation [2]).
• Positron emission tomography (PET): PET scans are sometimes used in the diagnosis and staging of DLBCL. They can help identify areas of high metabolic activity, which may indicate cancer cells (citation [7]).

Additional Tests

In some cases, additional tests may be necessary to confirm the diagnosis or assess the extent of disease. These may include:

• Bone marrow examination: A bone marrow examination may be performed to evaluate for any involvement of the bone marrow by DLBCL (citation [5]).
• Microscopic evaluation of pleural fluid, ascitic fluid, and cerebrospinal fluid: In rare cases, microscopic evaluation of these fluids may be necessary to confirm the diagnosis or assess the extent of disease (citation [5]).

High-Dose Chemotherapy and Stem Cell Transplantation

For patients with relapsed or refractory DLBCL, high-dose chemotherapy followed by stem cell transplantation can be a treatment option. This approach involves using high doses of chemotherapy to kill cancer cells, followed by the infusion of stem cells to help the body recover (citation [8]).

References:

[1] LS Raut et al., High-dose therapy followed by autologous stem cell transplant in relapsed or refractory DLBCL (2014) [2] Approach Considerations for Relapsed/Refractory DLBCL (2023) [3] Medical history and physical examination, blood tests, and radiologic imaging test (2022) [4] H Tilly et al., Diagnosis of relapsed or refractory DLBCL requires biopsy confirmation (2015) [5] R Iftikhar et al., Additional diagnostic tests for rare cases of DLBCL (2021) [6] Jun 25, 2024 — Diagnosis of relapsed or refractory (r/r) DLBCL requires biopsy confirmation in most cases. [7] JW Friedberg et al., Positron emission tomography (PET) in the diagnosis and staging of DLBCL (2011) [8] High-dose chemotherapy followed by stem cell transplantation for Relapsed/Refractory Diffuse Large B-Cell Lymphoma [9] The main way doctors diagnose DLBCL is to remove a swollen lymph node, or take a sample of tissue from it, and look at it under a microscope. [10] A doctor removes part or all of the swollen lymph node. They send it to the laboratory for a specialist to look at it under a microscope.

Relapsed or refractory diffuse large B-cell lymphoma (DLBCL) is a type of non-Hodgkin lymphoma that requires aggressive treatment.

Treatment Options

Several treatment options are available for patients with relapsed or refractory DLBCL:

• High-dose chemotherapy followed by stem cell transplantation: This is the standard of care for chemosensitive relapses in DLBCL. It involves administering high doses of chemotherapy to kill cancer cells, followed by a stem cell transplant to help the body recover.
• Autologous stem cell transplantation (ASCT): ASCT is a type of stem cell transplant where the patient's own stem cells are used. This treatment option has been shown to be effective in treating relapsed or refractory DLBCL.
• CAR-T cell therapy: CAR-T cell therapy involves using genetically modified T-cells to attack cancer cells. It has become a new standard treatment for patients with refractory or early relapsed DLBCL, based on the positive results of phase 3 trials [1][7].
• Immunotherapy: Immunotherapies such as polatuzumab vedotin, bendamustine and rituximab (pola-BR) have been approved for patients with R/R DLBCL after at least two prior therapies [6].

Other Treatment Options

In addition to the above treatment options, other treatments may be considered on a case-by-case basis. These include:

• Autologous bone marrow transplant: This involves using the patient's own bone marrow cells to help treat relapsed DLBCL.
• Chemotherapy: Chemotherapy may be used in combination with other treatments or as a standalone treatment for patients with relapsed or refractory DLBCL.

References

[1] AM García-Sancho, et al. CAR-T cell therapy has become the new standard treatment for patients with refractory or early relapsed DLBCL, based on the positive results of the phase 3 ZUMA trial [7].

[2] High-dose chemotherapy followed by stem cell transplantation can be used to treat patients with Relapsed/Refractory Diffuse Large B-Cell Lymphoma.

[3] Salvage high-dose chemotherapy followed by autologous stem cell transplantation is the standard of care for chemosensitive relapses in DLBCL [3].

[4] Historically, the treatment of relapsed/refractory (R/R) DLBCL has been salvage chemotherapy followed by autologous stem-cell transplant (ASCT) [4].

[5] You may receive an autologous bone marrow transplant, chemotherapy, or immunotherapy to help treat relapsed DLBCL. If you've achieved remission after successful treatment, it's possible that the cancer will not come back.

[6] The combination of polatuzumab vedotin, bendamustine and rituximab (pola-BR) was FDA approved for patients with R/R DLBCL after at least two prior therapies [6].

[7] CAR-T cell therapy has become the new standard treatment for patients with refractory or early relapsed DLBCL, based on the positive results of the phase 3 ZUMA trial [1][7].

[8] Although autologous stem cell transplantation (ASCT) consolidation remains the treatment of choice for patients with DLBCL, it is only recommended for young, fit patients.

The differential diagnosis of relapsed/refractory diffuse large B-cell lymphoma (DLBCL) involves considering various conditions that may present with similar symptoms and characteristics.

According to the search results, the differential diagnosis of DLBCL includes:

• Burkitt's lymphoma (BL)
• Hodgkin's lymphoma
• Anaplastic large cell lymphoma
• Gray-zone lymphomas (those that do not fit neatly into either the B-cell or T-cell categories)

These conditions can be distinguished from DLBCL through a combination of clinical evaluation, imaging studies, and histopathological examination.

In particular, Burkitt's lymphoma is a high-grade B-cell lymphoma that typically presents with rapid growth and widespread dissemination. It is often associated with a specific genetic abnormality (t(8;14)) and can be distinguished from DLBCL by its characteristic "starry sky" appearance under the microscope.

Hodgkin's lymphoma, on the other hand, is a distinct entity that typically presents with lymphadenopathy and systemic symptoms. It is characterized by the presence of Reed-Sternberg cells, which are not typically seen in DLBCL.

Anaplastic large cell lymphoma (ALCL) is another type of non-Hodgkin lymphoma that can be distinguished from DLBCL through its characteristic morphology and immunophenotype.

Gray-zone lymphomas, as the name suggests, fall into a gray area between B-cell and T-cell lymphomas. They are often characterized by a mixture of B-cell and T-cell markers and can be challenging to diagnose.

In terms of clinical management, it is essential to establish a definitive diagnosis before proceeding with treatment for relapsed/refractory DLBCL. This may involve performing a biopsy or other diagnostic procedures to confirm the presence of DLBCL and rule out other potential causes.

References:

• [6] Differential diagnosis of DLBCL includes Burkitt's lymphoma (BL), Hodgkin's lymphoma, anaplastic large cell lymphoma, and gray-zone lymphomas (those that do not fit neatly into either the B-cell or T-cell categories).
• [6] These conditions can be distinguished from DLBCL through a combination of clinical evaluation, imaging studies, and histopathological examination.
• [10] In patients who are suspected of having relapsed on the basis of imaging studies, the diagnosis should be confirmed by biopsy before proceeding to second-line treatment.