B Cell Lymphoma

The rapid rise of chimeric antigen receptor T (CAR T-cell) therapy has allowed hematologists to make great strides in treating aggressive cases of multiple myeloma and several types of lymphoma and leukemia. But patients with chronic lymphocytic leukemia (CLL), the most common leukemia in adults, have been left out.

Now there are encouraging signs that CLL could join the list of blood cancers that can be effectively treated by CAR T therapy. On another front, bispecific antibodies – which just received FDA approval to treat B-cell lymphoma – are being tested as treatments for CLL.

“These are the two immunotherapies that have the most potential right now,” said Ohio State University, Columbus, hematologist Kerry A. Rogers, MD, in an interview. She went on to say that these treatments could be a boon for patients with CLL who don’t respond well to targeted therapy drugs or are so young that those medications may not retain effectiveness throughout the patients’ lifespans.

As the American Cancer Society explains, CAR T therapy is a way to get T cells “to fight cancer by changing them in the lab so they can find and destroy cancer cells.” The cells are then returned to the patient.

As the National Cancer Institute says, “If all goes as planned, the CAR T cells will continue to multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill any cancer cells that harbor the target antigen on their surfaces.”

According to Dr. Rogers, CAR T therapy is less toxic than stem cell transplantation, a related treatment. That means older people can better tolerate it, including many CLL patients in their late 60s and beyond, she said. (Side effects of CAR T therapy include cytokine release syndrome, nervous system impairment, and weakening of the immune system.)

Thus far, CAR T therapy has been approved by the U.S. Food and Drug Administration to treat lymphomas, some forms of leukemia, and multiple myeloma. “Despite the excitement around these therapies, they lead to long-term survival in fewer than half of the patients treated,” cautions the National Cancer Institute, which also notes their high cost: more than $450,000 in one case.

CAR T therapy is not FDA-approved for CLL. “There are many reasons why CAR T is less effective in patients with CLL versus other lymphomas,” said Lee Greenberger, PhD, chief scientific officer of the Leukemia & Lymphoma Society, in an interview. “For one, many patients with heavily pretreated CLL – prior to any use of CAR T – have mutations that are known to be difficult to treat. Dysfunctional T cells are also common in patients with CLL, and there’s often a lower number of available T-cells to manufacture.”

The results of a phase 1/2 trial released in August 2023 offered new insight about CAR T for CLL. In the open-label trial reported in The Lancet, 117 U.S. patients with CLL or small lymphocytic lymphoma underwent a form of CAR T therapy called lisocabtagene maraleucel after failing treatment with two lines of therapy, including a Bruton´s tyrosine kinase inhibitor. Among 49 patients at a specific dose, “the rate of complete response or remission (including with incomplete marrow recovery) was statistically significant at 18%,” the researchers reported. A total of 51 patients in the entire study died.

The rate of undetectable minimal residual disease blood was 64%. That rate is impressive, said University of Texas MD Anderson Cancer Center leukemia specialist Nitin Jain, MD, in an interview. It’s not nearly as high as researchers have seen in other disease settings, but it’s “a good, good thing for these patients. We’ll have to see in the longer follow-up how these patients fare 2, 3, or 4 years down the line.”

Dr. Rogers, the Ohio physician, said doctors had hoped durable benefit in the Lancet study would be more impressive. An important factor limiting its value may be the aggressiveness of the disease in patients who have already failed several treatments, she said. “The efficacy of CAR T might be improved by giving it as an earlier line of therapy before the CLL has become this aggressive. But it’s difficult to propose that you should use this before a Bruton´s tyrosine kinase inhibitor or venetoclax because it’s expensive and difficult.”

What’s next for CART T research in CLL? Understanding the best timing for treatment will be key, Dr. Rogers said.

The Leukemia & Lymphoma Society’s Dr. Greenberger predicted that “we will begin to see CAR T explored in CLL patients whose disease has a high risk of failing approved agents, such as Bruton´s tyrosine kinase and B cell lymphoma 2 inhibitors. However, CLL patients may still receive prior therapy with more effective Bruton’s tyrosine kinase or B cell lymphoma 2 inhibitors in the future before using CAR T. This will likely be heightened as more Bruton´s tyrosine kinase inhibitors become generic in the next 5 to 10 years and, hopefully, less expensive than CAR T therapy.”

In the big picture, he said, “treatment of CLL with CAR T is possible, but still needs significant improvements if it is to become a mainline therapy in the future.”

CAR T therapy remains available via clinical trials, and Dr. Rogers said it is “currently an important option for patients whose CLL has become resistant to standard targeted agents. We can certainly expect to extend someone’s expected survival by years if they have a favorable response.” She acknowledged that the cost is quite high, but noted that targeted therapies are also expensive, especially over the long term. They can run to $10,000-$20,000 a month. Bispecific antibodies are also being explored as potential therapy for CLL. “They’re really exciting,” Dr. Rogers said, with the potential to spur responses similar to those from CAR T therapy.

A 2022 review described these drugs as “molecules that combine antibody-directed therapies with cellular mediated immunotherapy.” The FDA explains that “by targeting two antigens or epitopes, they can cause multiple physiological or antitumor responses, which may be independent or connected.”

According to Dr. Greenberger, many bispecifics are in clinical trials now. However, “in the context of CLL, actually, the data is actually very, very limited. The development is just starting, and there are phase 1 and phase 2 trials ongoing.”

But data from lymphoma trials are encouraging, he said, and bispecifics “are actually looking as good as CAR T in some settings.”

Regimens can be a challenge for patients taking bispecifics, Dr. Greenberger said. “Repeat dosing with a step-up dosing approach to start is typically required when treating lymphoma.”

On the other hand, Dr. Rogers noted that antibody treatment can be easier for hematologists to arrange than CAR T therapy and stem cell transplants. “From an administrative side, there’s not as many things you need to have set up. So it’s able to be administered in a wider variety of settings,” she said,

Bispecific side effects include cytokine release syndrome and neurotoxicity as well as infusion reactions, Dr. Greenberger said, adding that “I would not exclude cost as a challenge.”

According to Formulary Watch, the bispecific Columvi (glofitamab-gxbm), which recently gained FDA approval to treat diffuse large B-cell lymphoma, is estimated to cost $350,000 for an 8.5-month round of treatment. Reuters reported that the bispecific Talvey (talquetamab-tgvs), which just received FDA approval to treat multiple myeloma, is estimated to cost $270,000-$360,000 for 6-8 months of treatment.

For now, bispecific trials “are mostly now reserved for patients with CLL who become resistant to our current standard targeted agents,” Dr. Rogers said. “It’s a little unclear if you can do CAR T therapy first and then bispecifics, or bispecifics and then CAR T therapy.”

What’s coming next for bispecifics? “On the horizon is better ease of administration, which is already being addressed by subcutaneous dosing for some bispecifics in lymphomas,” Dr. Greenberger said. “There’s also the possibility of combining bispecifics with conventional therapy.”

Dr. Rogers discloses ties with Genentech, AbbVie, Novartis, AstraZeneca, Janssen, Pharmacyclics, Beigene, and LOXO@Lilly. Dr. Greenberger discloses employment with the Leukemia & Lymphoma Society, which supports academic grants and a venture philanthropy via the Therapy Acceleration Program.

Dr. Jain reports ties with Pharmacyclics, AbbVie, Genentech, AstraZeneca, Pfizer, and numerous other disclosures.
 

The rapid rise of chimeric antigen receptor T (CAR T-cell) therapy has allowed hematologists to make great strides in treating aggressive cases of multiple myeloma and several types of lymphoma and leukemia. But patients with chronic lymphocytic leukemia (CLL), the most common leukemia in adults, have been left out.

Now there are encouraging signs that CLL could join the list of blood cancers that can be effectively treated by CAR T therapy. On another front, bispecific antibodies – which just received FDA approval to treat B-cell lymphoma – are being tested as treatments for CLL.

“These are the two immunotherapies that have the most potential right now,” said Ohio State University, Columbus, hematologist Kerry A. Rogers, MD, in an interview. She went on to say that these treatments could be a boon for patients with CLL who don’t respond well to targeted therapy drugs or are so young that those medications may not retain effectiveness throughout the patients’ lifespans.

As the American Cancer Society explains, CAR T therapy is a way to get T cells “to fight cancer by changing them in the lab so they can find and destroy cancer cells.” The cells are then returned to the patient.

As the National Cancer Institute says, “If all goes as planned, the CAR T cells will continue to multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill any cancer cells that harbor the target antigen on their surfaces.”

According to Dr. Rogers, CAR T therapy is less toxic than stem cell transplantation, a related treatment. That means older people can better tolerate it, including many CLL patients in their late 60s and beyond, she said. (Side effects of CAR T therapy include cytokine release syndrome, nervous system impairment, and weakening of the immune system.)

Thus far, CAR T therapy has been approved by the U.S. Food and Drug Administration to treat lymphomas, some forms of leukemia, and multiple myeloma. “Despite the excitement around these therapies, they lead to long-term survival in fewer than half of the patients treated,” cautions the National Cancer Institute, which also notes their high cost: more than $450,000 in one case.

CAR T therapy is not FDA-approved for CLL. “There are many reasons why CAR T is less effective in patients with CLL versus other lymphomas,” said Lee Greenberger, PhD, chief scientific officer of the Leukemia & Lymphoma Society, in an interview. “For one, many patients with heavily pretreated CLL – prior to any use of CAR T – have mutations that are known to be difficult to treat. Dysfunctional T cells are also common in patients with CLL, and there’s often a lower number of available T-cells to manufacture.”

The results of a phase 1/2 trial released in August 2023 offered new insight about CAR T for CLL. In the open-label trial reported in The Lancet, 117 U.S. patients with CLL or small lymphocytic lymphoma underwent a form of CAR T therapy called lisocabtagene maraleucel after failing treatment with two lines of therapy, including a Bruton´s tyrosine kinase inhibitor. Among 49 patients at a specific dose, “the rate of complete response or remission (including with incomplete marrow recovery) was statistically significant at 18%,” the researchers reported. A total of 51 patients in the entire study died.

The rate of undetectable minimal residual disease blood was 64%. That rate is impressive, said University of Texas MD Anderson Cancer Center leukemia specialist Nitin Jain, MD, in an interview. It’s not nearly as high as researchers have seen in other disease settings, but it’s “a good, good thing for these patients. We’ll have to see in the longer follow-up how these patients fare 2, 3, or 4 years down the line.”

Dr. Rogers, the Ohio physician, said doctors had hoped durable benefit in the Lancet study would be more impressive. An important factor limiting its value may be the aggressiveness of the disease in patients who have already failed several treatments, she said. “The efficacy of CAR T might be improved by giving it as an earlier line of therapy before the CLL has become this aggressive. But it’s difficult to propose that you should use this before a Bruton´s tyrosine kinase inhibitor or venetoclax because it’s expensive and difficult.”

What’s next for CART T research in CLL? Understanding the best timing for treatment will be key, Dr. Rogers said.

The Leukemia & Lymphoma Society’s Dr. Greenberger predicted that “we will begin to see CAR T explored in CLL patients whose disease has a high risk of failing approved agents, such as Bruton´s tyrosine kinase and B cell lymphoma 2 inhibitors. However, CLL patients may still receive prior therapy with more effective Bruton’s tyrosine kinase or B cell lymphoma 2 inhibitors in the future before using CAR T. This will likely be heightened as more Bruton´s tyrosine kinase inhibitors become generic in the next 5 to 10 years and, hopefully, less expensive than CAR T therapy.”

In the big picture, he said, “treatment of CLL with CAR T is possible, but still needs significant improvements if it is to become a mainline therapy in the future.”

CAR T therapy remains available via clinical trials, and Dr. Rogers said it is “currently an important option for patients whose CLL has become resistant to standard targeted agents. We can certainly expect to extend someone’s expected survival by years if they have a favorable response.” She acknowledged that the cost is quite high, but noted that targeted therapies are also expensive, especially over the long term. They can run to $10,000-$20,000 a month. Bispecific antibodies are also being explored as potential therapy for CLL. “They’re really exciting,” Dr. Rogers said, with the potential to spur responses similar to those from CAR T therapy.

A 2022 review described these drugs as “molecules that combine antibody-directed therapies with cellular mediated immunotherapy.” The FDA explains that “by targeting two antigens or epitopes, they can cause multiple physiological or antitumor responses, which may be independent or connected.”

According to Dr. Greenberger, many bispecifics are in clinical trials now. However, “in the context of CLL, actually, the data is actually very, very limited. The development is just starting, and there are phase 1 and phase 2 trials ongoing.”

But data from lymphoma trials are encouraging, he said, and bispecifics “are actually looking as good as CAR T in some settings.”

Regimens can be a challenge for patients taking bispecifics, Dr. Greenberger said. “Repeat dosing with a step-up dosing approach to start is typically required when treating lymphoma.”

On the other hand, Dr. Rogers noted that antibody treatment can be easier for hematologists to arrange than CAR T therapy and stem cell transplants. “From an administrative side, there’s not as many things you need to have set up. So it’s able to be administered in a wider variety of settings,” she said,

Bispecific side effects include cytokine release syndrome and neurotoxicity as well as infusion reactions, Dr. Greenberger said, adding that “I would not exclude cost as a challenge.”

According to Formulary Watch, the bispecific Columvi (glofitamab-gxbm), which recently gained FDA approval to treat diffuse large B-cell lymphoma, is estimated to cost $350,000 for an 8.5-month round of treatment. Reuters reported that the bispecific Talvey (talquetamab-tgvs), which just received FDA approval to treat multiple myeloma, is estimated to cost $270,000-$360,000 for 6-8 months of treatment.

For now, bispecific trials “are mostly now reserved for patients with CLL who become resistant to our current standard targeted agents,” Dr. Rogers said. “It’s a little unclear if you can do CAR T therapy first and then bispecifics, or bispecifics and then CAR T therapy.”

What’s coming next for bispecifics? “On the horizon is better ease of administration, which is already being addressed by subcutaneous dosing for some bispecifics in lymphomas,” Dr. Greenberger said. “There’s also the possibility of combining bispecifics with conventional therapy.”

Dr. Rogers discloses ties with Genentech, AbbVie, Novartis, AstraZeneca, Janssen, Pharmacyclics, Beigene, and LOXO@Lilly. Dr. Greenberger discloses employment with the Leukemia & Lymphoma Society, which supports academic grants and a venture philanthropy via the Therapy Acceleration Program.

Dr. Jain reports ties with Pharmacyclics, AbbVie, Genentech, AstraZeneca, Pfizer, and numerous other disclosures.
 

The rapid rise of chimeric antigen receptor T (CAR T-cell) therapy has allowed hematologists to make great strides in treating aggressive cases of multiple myeloma and several types of lymphoma and leukemia. But patients with chronic lymphocytic leukemia (CLL), the most common leukemia in adults, have been left out.

Now there are encouraging signs that CLL could join the list of blood cancers that can be effectively treated by CAR T therapy. On another front, bispecific antibodies – which just received FDA approval to treat B-cell lymphoma – are being tested as treatments for CLL.

“These are the two immunotherapies that have the most potential right now,” said Ohio State University, Columbus, hematologist Kerry A. Rogers, MD, in an interview. She went on to say that these treatments could be a boon for patients with CLL who don’t respond well to targeted therapy drugs or are so young that those medications may not retain effectiveness throughout the patients’ lifespans.

As the American Cancer Society explains, CAR T therapy is a way to get T cells “to fight cancer by changing them in the lab so they can find and destroy cancer cells.” The cells are then returned to the patient.

As the National Cancer Institute says, “If all goes as planned, the CAR T cells will continue to multiply in the patient’s body and, with guidance from their engineered receptor, recognize and kill any cancer cells that harbor the target antigen on their surfaces.”

According to Dr. Rogers, CAR T therapy is less toxic than stem cell transplantation, a related treatment. That means older people can better tolerate it, including many CLL patients in their late 60s and beyond, she said. (Side effects of CAR T therapy include cytokine release syndrome, nervous system impairment, and weakening of the immune system.)

Thus far, CAR T therapy has been approved by the U.S. Food and Drug Administration to treat lymphomas, some forms of leukemia, and multiple myeloma. “Despite the excitement around these therapies, they lead to long-term survival in fewer than half of the patients treated,” cautions the National Cancer Institute, which also notes their high cost: more than $450,000 in one case.

CAR T therapy is not FDA-approved for CLL. “There are many reasons why CAR T is less effective in patients with CLL versus other lymphomas,” said Lee Greenberger, PhD, chief scientific officer of the Leukemia & Lymphoma Society, in an interview. “For one, many patients with heavily pretreated CLL – prior to any use of CAR T – have mutations that are known to be difficult to treat. Dysfunctional T cells are also common in patients with CLL, and there’s often a lower number of available T-cells to manufacture.”

The results of a phase 1/2 trial released in August 2023 offered new insight about CAR T for CLL. In the open-label trial reported in The Lancet, 117 U.S. patients with CLL or small lymphocytic lymphoma underwent a form of CAR T therapy called lisocabtagene maraleucel after failing treatment with two lines of therapy, including a Bruton´s tyrosine kinase inhibitor. Among 49 patients at a specific dose, “the rate of complete response or remission (including with incomplete marrow recovery) was statistically significant at 18%,” the researchers reported. A total of 51 patients in the entire study died.

The rate of undetectable minimal residual disease blood was 64%. That rate is impressive, said University of Texas MD Anderson Cancer Center leukemia specialist Nitin Jain, MD, in an interview. It’s not nearly as high as researchers have seen in other disease settings, but it’s “a good, good thing for these patients. We’ll have to see in the longer follow-up how these patients fare 2, 3, or 4 years down the line.”

Dr. Rogers, the Ohio physician, said doctors had hoped durable benefit in the Lancet study would be more impressive. An important factor limiting its value may be the aggressiveness of the disease in patients who have already failed several treatments, she said. “The efficacy of CAR T might be improved by giving it as an earlier line of therapy before the CLL has become this aggressive. But it’s difficult to propose that you should use this before a Bruton´s tyrosine kinase inhibitor or venetoclax because it’s expensive and difficult.”

What’s next for CART T research in CLL? Understanding the best timing for treatment will be key, Dr. Rogers said.

The Leukemia & Lymphoma Society’s Dr. Greenberger predicted that “we will begin to see CAR T explored in CLL patients whose disease has a high risk of failing approved agents, such as Bruton´s tyrosine kinase and B cell lymphoma 2 inhibitors. However, CLL patients may still receive prior therapy with more effective Bruton’s tyrosine kinase or B cell lymphoma 2 inhibitors in the future before using CAR T. This will likely be heightened as more Bruton´s tyrosine kinase inhibitors become generic in the next 5 to 10 years and, hopefully, less expensive than CAR T therapy.”

In the big picture, he said, “treatment of CLL with CAR T is possible, but still needs significant improvements if it is to become a mainline therapy in the future.”

CAR T therapy remains available via clinical trials, and Dr. Rogers said it is “currently an important option for patients whose CLL has become resistant to standard targeted agents. We can certainly expect to extend someone’s expected survival by years if they have a favorable response.” She acknowledged that the cost is quite high, but noted that targeted therapies are also expensive, especially over the long term. They can run to $10,000-$20,000 a month. Bispecific antibodies are also being explored as potential therapy for CLL. “They’re really exciting,” Dr. Rogers said, with the potential to spur responses similar to those from CAR T therapy.

A 2022 review described these drugs as “molecules that combine antibody-directed therapies with cellular mediated immunotherapy.” The FDA explains that “by targeting two antigens or epitopes, they can cause multiple physiological or antitumor responses, which may be independent or connected.”

According to Dr. Greenberger, many bispecifics are in clinical trials now. However, “in the context of CLL, actually, the data is actually very, very limited. The development is just starting, and there are phase 1 and phase 2 trials ongoing.”

But data from lymphoma trials are encouraging, he said, and bispecifics “are actually looking as good as CAR T in some settings.”

Regimens can be a challenge for patients taking bispecifics, Dr. Greenberger said. “Repeat dosing with a step-up dosing approach to start is typically required when treating lymphoma.”

On the other hand, Dr. Rogers noted that antibody treatment can be easier for hematologists to arrange than CAR T therapy and stem cell transplants. “From an administrative side, there’s not as many things you need to have set up. So it’s able to be administered in a wider variety of settings,” she said,

Bispecific side effects include cytokine release syndrome and neurotoxicity as well as infusion reactions, Dr. Greenberger said, adding that “I would not exclude cost as a challenge.”

According to Formulary Watch, the bispecific Columvi (glofitamab-gxbm), which recently gained FDA approval to treat diffuse large B-cell lymphoma, is estimated to cost $350,000 for an 8.5-month round of treatment. Reuters reported that the bispecific Talvey (talquetamab-tgvs), which just received FDA approval to treat multiple myeloma, is estimated to cost $270,000-$360,000 for 6-8 months of treatment.

For now, bispecific trials “are mostly now reserved for patients with CLL who become resistant to our current standard targeted agents,” Dr. Rogers said. “It’s a little unclear if you can do CAR T therapy first and then bispecifics, or bispecifics and then CAR T therapy.”

What’s coming next for bispecifics? “On the horizon is better ease of administration, which is already being addressed by subcutaneous dosing for some bispecifics in lymphomas,” Dr. Greenberger said. “There’s also the possibility of combining bispecifics with conventional therapy.”

Dr. Rogers discloses ties with Genentech, AbbVie, Novartis, AstraZeneca, Janssen, Pharmacyclics, Beigene, and LOXO@Lilly. Dr. Greenberger discloses employment with the Leukemia & Lymphoma Society, which supports academic grants and a venture philanthropy via the Therapy Acceleration Program.

Dr. Jain reports ties with Pharmacyclics, AbbVie, Genentech, AstraZeneca, Pfizer, and numerous other disclosures.
 

Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma that is characterized by t(11;14) and cyclin D1 overexpression. It is also known to be clinically heterogenous, with disease presentations ranging from indolent to aggressive. Baseline risk can be determined on the basis of a combination of clinical and pathologic features. A key prognostic tool, for example, is the Mantle Cell Lymphoma International Prognostic Index-Combined (MIPI-c), which integrates the standard MIPI clinical factors (age, performance status, lactate dehydrogenase, and leukocyte count) with estimates of proliferation (Ki-67).¹ Other features, including the presence of TP53 alterations, have also been associated with poor outcomes, even with intensive therapy.²

Recently, a study aimed to further refine prognostication in MCL in order to identify high-risk patients that may be more likely to benefit from novel treatment strategies (Scheubeck et al). This retrospective study included 684 patients with MCL from the MCL-Younger and MCL-Elderly trials with evaluable data for Ki-67 or p53 expression (a surrogate for TP53 alterations). Patients were classified as having high-risk disease on the basis of a high-risk MIPI-c or p53 expression > 50% or as having low-risk disease on the basis of low, low-intermediate, or high-intermediate MIPI-c and p53 expression ≤ 50%. Patients with high-risk disease had significantly shorter median failure-free survival (1.1 vs 5.6 years; P < .0001) and overall survival (2.2 vs 13.2 years; P < .0001) compared with those with low-risk disease. The differences were confirmed in two validation cohorts from the Italian MCL0208 and Nordic-MCL4 trials. These data highlight the poor outcomes of conventional therapy in patients with high-risk MCL. Evaluation of novel approaches should be considered in these patients.

Bruton tyrosine kinase (BTK) inhibitors have been promising options for patients with MCL, including those with high-risk features. Acalabrutinib is a second-generation covalent BTK inhibitor that is approved by the US Food and Drug Administration for patients who have received at least one prior line of therapy. The final results of the single-arm, phase 2 ACE-LY-004 study recently demonstrated long-term safety and efficacy in patients with relapsed/refractory MCL (Le Gouill et al). The overall and complete response rates were 81.5% (95% CI 73.5%-87.9%) and 47.6% (95% CI 38.5%-56.7%), respectively. After a 38.1-month median follow-up, the median duration of response and progression-free survival were 28.6 months (95% CI 17.5-39.1) and 22.0 months (95% CI 16.6-33.3), respectively. Responses were also seen in patients with high-risk features, including blastoid morphology, high-risk MIPI score, and high Ki-67. No new safety signals were observed. This study confirms the role of BTK inhibitors in MCL and providers longer-term estimates of response. Evaluation of BTK inhibitors in earlier lines of therapy and in combination with other agents are ongoing.

Although the majority of patients with MCL will have favorable responses to initial therapy, those with high-risk features, particularly TP53 aberrations, have poor outcomes with standard approaches. Despite a growing number of treatment options in the relapsed setting, such as targeted therapies and chimeric antigen receptor (CAR) T-cell therapy, relapses remain common. Allogenic stem cell transplantation can be associated with prolonged response for patients with relapsed MCL, though it has the potential for significant treatment-associated toxicity.

Recently, prolonged follow-up of a retrospective cohort of patients with MCL, including a subset with TP53 aberrations, was reported (Lew et al). Thirty-six patients with MCL were included, including 13 with TP53-mutated disease. A subset of patients (61%) received an allogeneic transplant in first remission. The estimated overall survival rates after allogenic transplant were 56% (95% CI 36%-72%) at 10 years for the overall cohort and 59% (95% CI 21%-75%) at 4 years for patients with TP53-mutated disease at median follow-ups of 10.8 and 4.2 years, respectively. No relapses were observed in the TP53-mutated subset beyond 6 months after transplantation. These data suggest a potentially curative option for patients with high-risk MCL. Given the availability of CAR T-cell therapy, the optimal timing of allogenic stem cell transplant has become less clear for patients with TP53-mutant disease. Although this study was small and retrospective, these data are encouraging for patients with high-risk disease.

Additional References

1.            Hoster E, Rosenwald A, Berger F, et al. Prognostic value of Ki-67 index, cytology, and growth pattern in mantle-cell lymphoma: Results from randomized trials of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2016;34:1386-1394. doi: 10.1200/JCO.2015.63.8387

2.            Eskelund CW, Dahl C, Hansen JW, et al. TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy. Blood. 2017;130:1903-1910. doi: 10.1182/blood-2017-04-77973

Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma that is characterized by t(11;14) and cyclin D1 overexpression. It is also known to be clinically heterogenous, with disease presentations ranging from indolent to aggressive. Baseline risk can be determined on the basis of a combination of clinical and pathologic features. A key prognostic tool, for example, is the Mantle Cell Lymphoma International Prognostic Index-Combined (MIPI-c), which integrates the standard MIPI clinical factors (age, performance status, lactate dehydrogenase, and leukocyte count) with estimates of proliferation (Ki-67).¹ Other features, including the presence of TP53 alterations, have also been associated with poor outcomes, even with intensive therapy.²

Recently, a study aimed to further refine prognostication in MCL in order to identify high-risk patients that may be more likely to benefit from novel treatment strategies (Scheubeck et al). This retrospective study included 684 patients with MCL from the MCL-Younger and MCL-Elderly trials with evaluable data for Ki-67 or p53 expression (a surrogate for TP53 alterations). Patients were classified as having high-risk disease on the basis of a high-risk MIPI-c or p53 expression > 50% or as having low-risk disease on the basis of low, low-intermediate, or high-intermediate MIPI-c and p53 expression ≤ 50%. Patients with high-risk disease had significantly shorter median failure-free survival (1.1 vs 5.6 years; P < .0001) and overall survival (2.2 vs 13.2 years; P < .0001) compared with those with low-risk disease. The differences were confirmed in two validation cohorts from the Italian MCL0208 and Nordic-MCL4 trials. These data highlight the poor outcomes of conventional therapy in patients with high-risk MCL. Evaluation of novel approaches should be considered in these patients.

Bruton tyrosine kinase (BTK) inhibitors have been promising options for patients with MCL, including those with high-risk features. Acalabrutinib is a second-generation covalent BTK inhibitor that is approved by the US Food and Drug Administration for patients who have received at least one prior line of therapy. The final results of the single-arm, phase 2 ACE-LY-004 study recently demonstrated long-term safety and efficacy in patients with relapsed/refractory MCL (Le Gouill et al). The overall and complete response rates were 81.5% (95% CI 73.5%-87.9%) and 47.6% (95% CI 38.5%-56.7%), respectively. After a 38.1-month median follow-up, the median duration of response and progression-free survival were 28.6 months (95% CI 17.5-39.1) and 22.0 months (95% CI 16.6-33.3), respectively. Responses were also seen in patients with high-risk features, including blastoid morphology, high-risk MIPI score, and high Ki-67. No new safety signals were observed. This study confirms the role of BTK inhibitors in MCL and providers longer-term estimates of response. Evaluation of BTK inhibitors in earlier lines of therapy and in combination with other agents are ongoing.

Although the majority of patients with MCL will have favorable responses to initial therapy, those with high-risk features, particularly TP53 aberrations, have poor outcomes with standard approaches. Despite a growing number of treatment options in the relapsed setting, such as targeted therapies and chimeric antigen receptor (CAR) T-cell therapy, relapses remain common. Allogenic stem cell transplantation can be associated with prolonged response for patients with relapsed MCL, though it has the potential for significant treatment-associated toxicity.

Recently, prolonged follow-up of a retrospective cohort of patients with MCL, including a subset with TP53 aberrations, was reported (Lew et al). Thirty-six patients with MCL were included, including 13 with TP53-mutated disease. A subset of patients (61%) received an allogeneic transplant in first remission. The estimated overall survival rates after allogenic transplant were 56% (95% CI 36%-72%) at 10 years for the overall cohort and 59% (95% CI 21%-75%) at 4 years for patients with TP53-mutated disease at median follow-ups of 10.8 and 4.2 years, respectively. No relapses were observed in the TP53-mutated subset beyond 6 months after transplantation. These data suggest a potentially curative option for patients with high-risk MCL. Given the availability of CAR T-cell therapy, the optimal timing of allogenic stem cell transplant has become less clear for patients with TP53-mutant disease. Although this study was small and retrospective, these data are encouraging for patients with high-risk disease.

Additional References

1.            Hoster E, Rosenwald A, Berger F, et al. Prognostic value of Ki-67 index, cytology, and growth pattern in mantle-cell lymphoma: Results from randomized trials of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2016;34:1386-1394. doi: 10.1200/JCO.2015.63.8387

2.            Eskelund CW, Dahl C, Hansen JW, et al. TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy. Blood. 2017;130:1903-1910. doi: 10.1182/blood-2017-04-77973

Mantle cell lymphoma (MCL) is a rare subtype of non-Hodgkin lymphoma that is characterized by t(11;14) and cyclin D1 overexpression. It is also known to be clinically heterogenous, with disease presentations ranging from indolent to aggressive. Baseline risk can be determined on the basis of a combination of clinical and pathologic features. A key prognostic tool, for example, is the Mantle Cell Lymphoma International Prognostic Index-Combined (MIPI-c), which integrates the standard MIPI clinical factors (age, performance status, lactate dehydrogenase, and leukocyte count) with estimates of proliferation (Ki-67).¹ Other features, including the presence of TP53 alterations, have also been associated with poor outcomes, even with intensive therapy.²

Recently, a study aimed to further refine prognostication in MCL in order to identify high-risk patients that may be more likely to benefit from novel treatment strategies (Scheubeck et al). This retrospective study included 684 patients with MCL from the MCL-Younger and MCL-Elderly trials with evaluable data for Ki-67 or p53 expression (a surrogate for TP53 alterations). Patients were classified as having high-risk disease on the basis of a high-risk MIPI-c or p53 expression > 50% or as having low-risk disease on the basis of low, low-intermediate, or high-intermediate MIPI-c and p53 expression ≤ 50%. Patients with high-risk disease had significantly shorter median failure-free survival (1.1 vs 5.6 years; P < .0001) and overall survival (2.2 vs 13.2 years; P < .0001) compared with those with low-risk disease. The differences were confirmed in two validation cohorts from the Italian MCL0208 and Nordic-MCL4 trials. These data highlight the poor outcomes of conventional therapy in patients with high-risk MCL. Evaluation of novel approaches should be considered in these patients.

Bruton tyrosine kinase (BTK) inhibitors have been promising options for patients with MCL, including those with high-risk features. Acalabrutinib is a second-generation covalent BTK inhibitor that is approved by the US Food and Drug Administration for patients who have received at least one prior line of therapy. The final results of the single-arm, phase 2 ACE-LY-004 study recently demonstrated long-term safety and efficacy in patients with relapsed/refractory MCL (Le Gouill et al). The overall and complete response rates were 81.5% (95% CI 73.5%-87.9%) and 47.6% (95% CI 38.5%-56.7%), respectively. After a 38.1-month median follow-up, the median duration of response and progression-free survival were 28.6 months (95% CI 17.5-39.1) and 22.0 months (95% CI 16.6-33.3), respectively. Responses were also seen in patients with high-risk features, including blastoid morphology, high-risk MIPI score, and high Ki-67. No new safety signals were observed. This study confirms the role of BTK inhibitors in MCL and providers longer-term estimates of response. Evaluation of BTK inhibitors in earlier lines of therapy and in combination with other agents are ongoing.

Although the majority of patients with MCL will have favorable responses to initial therapy, those with high-risk features, particularly TP53 aberrations, have poor outcomes with standard approaches. Despite a growing number of treatment options in the relapsed setting, such as targeted therapies and chimeric antigen receptor (CAR) T-cell therapy, relapses remain common. Allogenic stem cell transplantation can be associated with prolonged response for patients with relapsed MCL, though it has the potential for significant treatment-associated toxicity.

Recently, prolonged follow-up of a retrospective cohort of patients with MCL, including a subset with TP53 aberrations, was reported (Lew et al). Thirty-six patients with MCL were included, including 13 with TP53-mutated disease. A subset of patients (61%) received an allogeneic transplant in first remission. The estimated overall survival rates after allogenic transplant were 56% (95% CI 36%-72%) at 10 years for the overall cohort and 59% (95% CI 21%-75%) at 4 years for patients with TP53-mutated disease at median follow-ups of 10.8 and 4.2 years, respectively. No relapses were observed in the TP53-mutated subset beyond 6 months after transplantation. These data suggest a potentially curative option for patients with high-risk MCL. Given the availability of CAR T-cell therapy, the optimal timing of allogenic stem cell transplant has become less clear for patients with TP53-mutant disease. Although this study was small and retrospective, these data are encouraging for patients with high-risk disease.

Additional References

1.            Hoster E, Rosenwald A, Berger F, et al. Prognostic value of Ki-67 index, cytology, and growth pattern in mantle-cell lymphoma: Results from randomized trials of the European Mantle Cell Lymphoma Network. J Clin Oncol. 2016;34:1386-1394. doi: 10.1200/JCO.2015.63.8387

2.            Eskelund CW, Dahl C, Hansen JW, et al. TP53 mutations identify younger mantle cell lymphoma patients who do not benefit from intensive chemoimmunotherapy. Blood. 2017;130:1903-1910. doi: 10.1182/blood-2017-04-77973

Back in 1997, a young Stanford (Calif.) University student named Christopher Flowers made his debut in the medical literature with a Nature Medicine report that called out the pharmaceutical industry for overlooking the crucial role of clinical investigators in drug development.

“My research uncovered a series of physicians who served as ‘clinical champions’ and dramatically sped the process of drug development,” Dr. Flowers recalled in an interview. “This early career research inspired me to become the type of clinical champion that I uncovered.”

MD Anderson Cancer Center

Over his career, hematologist-oncologist Dr. Flowers has developed lifesaving therapies for lymphoma, which has transformed into a highly treatable and even curable disease. He’s listed as a coauthor of hundreds of peer-reviewed cancer studies, reports, and medical society guidelines. And he’s revealed stark disparities in blood cancer care: His research shows that non-White patients suffer from worse outcomes, regardless of factors like income and insurance coverage.

The University of Texas MD Anderson Cancer Center, Houston, recently named physician-scientist Dr. Flowers as division head of cancer medicine, a position he’s held on an interim basis. As of Sept. 1, he will permanently oversee 300 faculty and more than 2,000 staff members.
 

A running start in Seattle

For Dr. Flowers, track and field is a sport that runs in the family. His grandfather was a top runner in both high school and college, and both Dr. Flowers and his brother ran competitively in Seattle, where they grew up. But Dr. Flowers chose a career in oncology, earning a medical degree at Stanford and master’s degrees at both Stanford and the University of Washington, Seattle.

The late Kenneth Melmon, MD, a groundbreaking pharmacologist, was a major influence. “He was one of the first people that I met when I began as an undergraduate at Stanford. We grew to be long-standing friends, and he demonstrated what outstanding mentorship looks like. In our research collaboration, we investigated the work of Dr. Gertrude Elion and Dr. George Hitchings involving the translation of pharmacological data from cellular and animal models to clinically useful drugs including 6-mercaptopurine, allopurinol, azathioprine, acyclovir, and zidovudine.”

The late Oliver Press, MD, a blood cancer specialist, inspired Dr. Flower’s interest in lymphoma. “I began work with him during an internship at the University of Washington. Ollie was a great inspiration and a key leader in the development of innovative therapies for lymphoma. He embodied the role of a clinical champion translating work in radioimmunotherapy to new therapeutics for patients with lymphomas. Working with him ultimately led me to pursue a career in hematology and oncology with a focus on the care for patients with lymphomas.”
 

Career blooms as lymphoma care advances

Dr. Flowers went on to Emory University, Atlanta, where he served as scientific director of the Research Informatics Shared Resource and a faculty member in the department of biomedical informatics. “I applied my training in informatics and my clinical expertise to support active grants from the Burroughs Wellcome Fund for Innovation in Regulatory Science and from the National Cancer Institute to develop informatics tools for pathology image analysis and prognostic modeling.”

For 13 years, he also served the Winship Cancer Institute as director of the Emory Healthcare lymphoma program (where his patients included Kansas City Chiefs football star Eric Berry), and for 4 years as scientific director of research informatics. Meanwhile, Dr. Flowers helped develop national practice guidelines for the American Society of Clinical Oncology, the American Cancer Society, and the American College of Radiology. He also chaired the ASCO guideline on management of febrile neutropenia.

In 2019, MD Anderson hired Dr. Flowers as chair of the department of lymphoma/myeloma. A year later, he was appointed division head ad interim for cancer medicine.

“Chris is a unique leader who expertly combines mentorship, sponsorship, and bidirectional open, honest communication,” said Sairah Ahmed, MD, associate professor of lymphoma at MD Anderson. “He doesn’t just empower his team to reach their goals. He also inspires those around him to turn vision into reality.”

As Dr. Flowers noted, many patients with lymphoma are now able to recover and live normal lives. He himself played a direct role himself in boosting lifespans.

“I have been fortunate to play a role in the development of several treatments that have led to advances in first-line therapy for patients with aggressive lymphomas. I partnered with others at MD Anderson, including Dr. Sattva Neelapu and Dr. Jason Westin, who have developed novel therapies like chimeric antigen receptor T-cell therapy for patients with relapse lymphomas,” he said. “Leaders in the field at MD Anderson like Dr. Michael Wang have developed new oral treatments for patients with rare lymphoma subtypes like mantle cell lymphoma. Other colleagues such as Dr. Nathan Fowler and Dr. Loretta Nastoupil have focused on the care for patients with indolent lymphomas and developed less-toxic therapies that are now in common use.”
 

Exposing the disparities in blood cancer care

Dr. Flowers, who’s African American, has also been a leader in health disparity research. In 2016, for example, he was coauthor of a study into non-Hodgkin’s lymphoma that revealed that Blacks in the United States have dramatically lower survival rates than Whites. The 10-year survival rate for Black women with chronic lymphocytic leukemia was just 47%, for example, compared with 66% for White females. “Although incidence rates of lymphoid neoplasms are generally higher among Whites, Black men tend to have poorer survival,” Dr. Flowers and colleagues wrote.

In a 2021 report for the ASCO Educational Book, Dr. Flowers and hematologist-oncologist Demetria Smith-Graziani, MD, now with Emory University, explored disparities across blood cancers and barriers to minority enrollment in clinical trials. “Some approaches that clinicians can apply to address these disparities include increasing systems-level awareness, improving access to care, and reducing biases in clinical setting,” the authors wrote.

Luis Malpica Castillo, MD, assistant professor of lymphoma at MD Anderson Cancer Center, lauded the work of Dr. Flowers in expanding opportunities for minority patients with the disease.

“During the past years, Dr. Flowers’ work has not only had a positive impact on the Texan community, but minority populations living with cancer in the United States and abroad,” he said. “Currently, we are implementing cancer care networks aimed to increase diversity in clinical trials by enrolling a larger number of Hispanic and African American patients, who otherwise may not have benefited from novel therapies. The ultimate goal is to provide high-quality care to all patients living with cancer.”

In addition to his research work, Dr. Flowers is an advocate for diversity within the hematology community. He’s a founding member and former chair of the American Society of Hematology’s Committee on Diversity, Equity and Inclusion (formerly the Committee on Promoting Diversity), and he helped develop the society’s Minority Recruitment Initiative.

What’s next for Dr. Flowers? For one, he plans to continue working as a mentor; he received the ASH Mentor Award in honor of his service in 2022. “I am strongly committed to increasing the number of tenure-track investigators trained in clinical and translational cancer research and to promote their career development.”

And he looks forward to helping develop MD Anderson’s recently announced $2.5 billion hospital in Austin. “This will extend the exceptional care that we provide as the No. 1 cancer center in the United States,” he said. “It will also create new opportunities for research and collaboration with experts at UT Austin.”

When he’s not in clinic, Dr. Flowers embraces his lifelong love of speeding through life on his own two feet. He’s even inspired his children to share his passion. “I run most days of the week,” he said. “Running provides a great opportunity to think and process new research ideas, work through leadership challenges, and sometimes just to relax and let go of the day.”

Back in 1997, a young Stanford (Calif.) University student named Christopher Flowers made his debut in the medical literature with a Nature Medicine report that called out the pharmaceutical industry for overlooking the crucial role of clinical investigators in drug development.

“My research uncovered a series of physicians who served as ‘clinical champions’ and dramatically sped the process of drug development,” Dr. Flowers recalled in an interview. “This early career research inspired me to become the type of clinical champion that I uncovered.”

MD Anderson Cancer Center

Over his career, hematologist-oncologist Dr. Flowers has developed lifesaving therapies for lymphoma, which has transformed into a highly treatable and even curable disease. He’s listed as a coauthor of hundreds of peer-reviewed cancer studies, reports, and medical society guidelines. And he’s revealed stark disparities in blood cancer care: His research shows that non-White patients suffer from worse outcomes, regardless of factors like income and insurance coverage.

The University of Texas MD Anderson Cancer Center, Houston, recently named physician-scientist Dr. Flowers as division head of cancer medicine, a position he’s held on an interim basis. As of Sept. 1, he will permanently oversee 300 faculty and more than 2,000 staff members.
 

A running start in Seattle

For Dr. Flowers, track and field is a sport that runs in the family. His grandfather was a top runner in both high school and college, and both Dr. Flowers and his brother ran competitively in Seattle, where they grew up. But Dr. Flowers chose a career in oncology, earning a medical degree at Stanford and master’s degrees at both Stanford and the University of Washington, Seattle.

The late Kenneth Melmon, MD, a groundbreaking pharmacologist, was a major influence. “He was one of the first people that I met when I began as an undergraduate at Stanford. We grew to be long-standing friends, and he demonstrated what outstanding mentorship looks like. In our research collaboration, we investigated the work of Dr. Gertrude Elion and Dr. George Hitchings involving the translation of pharmacological data from cellular and animal models to clinically useful drugs including 6-mercaptopurine, allopurinol, azathioprine, acyclovir, and zidovudine.”

The late Oliver Press, MD, a blood cancer specialist, inspired Dr. Flower’s interest in lymphoma. “I began work with him during an internship at the University of Washington. Ollie was a great inspiration and a key leader in the development of innovative therapies for lymphoma. He embodied the role of a clinical champion translating work in radioimmunotherapy to new therapeutics for patients with lymphomas. Working with him ultimately led me to pursue a career in hematology and oncology with a focus on the care for patients with lymphomas.”
 

Career blooms as lymphoma care advances

Dr. Flowers went on to Emory University, Atlanta, where he served as scientific director of the Research Informatics Shared Resource and a faculty member in the department of biomedical informatics. “I applied my training in informatics and my clinical expertise to support active grants from the Burroughs Wellcome Fund for Innovation in Regulatory Science and from the National Cancer Institute to develop informatics tools for pathology image analysis and prognostic modeling.”

For 13 years, he also served the Winship Cancer Institute as director of the Emory Healthcare lymphoma program (where his patients included Kansas City Chiefs football star Eric Berry), and for 4 years as scientific director of research informatics. Meanwhile, Dr. Flowers helped develop national practice guidelines for the American Society of Clinical Oncology, the American Cancer Society, and the American College of Radiology. He also chaired the ASCO guideline on management of febrile neutropenia.

In 2019, MD Anderson hired Dr. Flowers as chair of the department of lymphoma/myeloma. A year later, he was appointed division head ad interim for cancer medicine.

“Chris is a unique leader who expertly combines mentorship, sponsorship, and bidirectional open, honest communication,” said Sairah Ahmed, MD, associate professor of lymphoma at MD Anderson. “He doesn’t just empower his team to reach their goals. He also inspires those around him to turn vision into reality.”

As Dr. Flowers noted, many patients with lymphoma are now able to recover and live normal lives. He himself played a direct role himself in boosting lifespans.

“I have been fortunate to play a role in the development of several treatments that have led to advances in first-line therapy for patients with aggressive lymphomas. I partnered with others at MD Anderson, including Dr. Sattva Neelapu and Dr. Jason Westin, who have developed novel therapies like chimeric antigen receptor T-cell therapy for patients with relapse lymphomas,” he said. “Leaders in the field at MD Anderson like Dr. Michael Wang have developed new oral treatments for patients with rare lymphoma subtypes like mantle cell lymphoma. Other colleagues such as Dr. Nathan Fowler and Dr. Loretta Nastoupil have focused on the care for patients with indolent lymphomas and developed less-toxic therapies that are now in common use.”
 

Exposing the disparities in blood cancer care

Dr. Flowers, who’s African American, has also been a leader in health disparity research. In 2016, for example, he was coauthor of a study into non-Hodgkin’s lymphoma that revealed that Blacks in the United States have dramatically lower survival rates than Whites. The 10-year survival rate for Black women with chronic lymphocytic leukemia was just 47%, for example, compared with 66% for White females. “Although incidence rates of lymphoid neoplasms are generally higher among Whites, Black men tend to have poorer survival,” Dr. Flowers and colleagues wrote.

In a 2021 report for the ASCO Educational Book, Dr. Flowers and hematologist-oncologist Demetria Smith-Graziani, MD, now with Emory University, explored disparities across blood cancers and barriers to minority enrollment in clinical trials. “Some approaches that clinicians can apply to address these disparities include increasing systems-level awareness, improving access to care, and reducing biases in clinical setting,” the authors wrote.

Luis Malpica Castillo, MD, assistant professor of lymphoma at MD Anderson Cancer Center, lauded the work of Dr. Flowers in expanding opportunities for minority patients with the disease.

“During the past years, Dr. Flowers’ work has not only had a positive impact on the Texan community, but minority populations living with cancer in the United States and abroad,” he said. “Currently, we are implementing cancer care networks aimed to increase diversity in clinical trials by enrolling a larger number of Hispanic and African American patients, who otherwise may not have benefited from novel therapies. The ultimate goal is to provide high-quality care to all patients living with cancer.”

In addition to his research work, Dr. Flowers is an advocate for diversity within the hematology community. He’s a founding member and former chair of the American Society of Hematology’s Committee on Diversity, Equity and Inclusion (formerly the Committee on Promoting Diversity), and he helped develop the society’s Minority Recruitment Initiative.

What’s next for Dr. Flowers? For one, he plans to continue working as a mentor; he received the ASH Mentor Award in honor of his service in 2022. “I am strongly committed to increasing the number of tenure-track investigators trained in clinical and translational cancer research and to promote their career development.”

And he looks forward to helping develop MD Anderson’s recently announced $2.5 billion hospital in Austin. “This will extend the exceptional care that we provide as the No. 1 cancer center in the United States,” he said. “It will also create new opportunities for research and collaboration with experts at UT Austin.”

When he’s not in clinic, Dr. Flowers embraces his lifelong love of speeding through life on his own two feet. He’s even inspired his children to share his passion. “I run most days of the week,” he said. “Running provides a great opportunity to think and process new research ideas, work through leadership challenges, and sometimes just to relax and let go of the day.”

Back in 1997, a young Stanford (Calif.) University student named Christopher Flowers made his debut in the medical literature with a Nature Medicine report that called out the pharmaceutical industry for overlooking the crucial role of clinical investigators in drug development.

“My research uncovered a series of physicians who served as ‘clinical champions’ and dramatically sped the process of drug development,” Dr. Flowers recalled in an interview. “This early career research inspired me to become the type of clinical champion that I uncovered.”

MD Anderson Cancer Center

Over his career, hematologist-oncologist Dr. Flowers has developed lifesaving therapies for lymphoma, which has transformed into a highly treatable and even curable disease. He’s listed as a coauthor of hundreds of peer-reviewed cancer studies, reports, and medical society guidelines. And he’s revealed stark disparities in blood cancer care: His research shows that non-White patients suffer from worse outcomes, regardless of factors like income and insurance coverage.

The University of Texas MD Anderson Cancer Center, Houston, recently named physician-scientist Dr. Flowers as division head of cancer medicine, a position he’s held on an interim basis. As of Sept. 1, he will permanently oversee 300 faculty and more than 2,000 staff members.
 

A running start in Seattle

For Dr. Flowers, track and field is a sport that runs in the family. His grandfather was a top runner in both high school and college, and both Dr. Flowers and his brother ran competitively in Seattle, where they grew up. But Dr. Flowers chose a career in oncology, earning a medical degree at Stanford and master’s degrees at both Stanford and the University of Washington, Seattle.

The late Kenneth Melmon, MD, a groundbreaking pharmacologist, was a major influence. “He was one of the first people that I met when I began as an undergraduate at Stanford. We grew to be long-standing friends, and he demonstrated what outstanding mentorship looks like. In our research collaboration, we investigated the work of Dr. Gertrude Elion and Dr. George Hitchings involving the translation of pharmacological data from cellular and animal models to clinically useful drugs including 6-mercaptopurine, allopurinol, azathioprine, acyclovir, and zidovudine.”

The late Oliver Press, MD, a blood cancer specialist, inspired Dr. Flower’s interest in lymphoma. “I began work with him during an internship at the University of Washington. Ollie was a great inspiration and a key leader in the development of innovative therapies for lymphoma. He embodied the role of a clinical champion translating work in radioimmunotherapy to new therapeutics for patients with lymphomas. Working with him ultimately led me to pursue a career in hematology and oncology with a focus on the care for patients with lymphomas.”
 

Career blooms as lymphoma care advances

Dr. Flowers went on to Emory University, Atlanta, where he served as scientific director of the Research Informatics Shared Resource and a faculty member in the department of biomedical informatics. “I applied my training in informatics and my clinical expertise to support active grants from the Burroughs Wellcome Fund for Innovation in Regulatory Science and from the National Cancer Institute to develop informatics tools for pathology image analysis and prognostic modeling.”

For 13 years, he also served the Winship Cancer Institute as director of the Emory Healthcare lymphoma program (where his patients included Kansas City Chiefs football star Eric Berry), and for 4 years as scientific director of research informatics. Meanwhile, Dr. Flowers helped develop national practice guidelines for the American Society of Clinical Oncology, the American Cancer Society, and the American College of Radiology. He also chaired the ASCO guideline on management of febrile neutropenia.

In 2019, MD Anderson hired Dr. Flowers as chair of the department of lymphoma/myeloma. A year later, he was appointed division head ad interim for cancer medicine.

“Chris is a unique leader who expertly combines mentorship, sponsorship, and bidirectional open, honest communication,” said Sairah Ahmed, MD, associate professor of lymphoma at MD Anderson. “He doesn’t just empower his team to reach their goals. He also inspires those around him to turn vision into reality.”

As Dr. Flowers noted, many patients with lymphoma are now able to recover and live normal lives. He himself played a direct role himself in boosting lifespans.

“I have been fortunate to play a role in the development of several treatments that have led to advances in first-line therapy for patients with aggressive lymphomas. I partnered with others at MD Anderson, including Dr. Sattva Neelapu and Dr. Jason Westin, who have developed novel therapies like chimeric antigen receptor T-cell therapy for patients with relapse lymphomas,” he said. “Leaders in the field at MD Anderson like Dr. Michael Wang have developed new oral treatments for patients with rare lymphoma subtypes like mantle cell lymphoma. Other colleagues such as Dr. Nathan Fowler and Dr. Loretta Nastoupil have focused on the care for patients with indolent lymphomas and developed less-toxic therapies that are now in common use.”
 

Exposing the disparities in blood cancer care

Dr. Flowers, who’s African American, has also been a leader in health disparity research. In 2016, for example, he was coauthor of a study into non-Hodgkin’s lymphoma that revealed that Blacks in the United States have dramatically lower survival rates than Whites. The 10-year survival rate for Black women with chronic lymphocytic leukemia was just 47%, for example, compared with 66% for White females. “Although incidence rates of lymphoid neoplasms are generally higher among Whites, Black men tend to have poorer survival,” Dr. Flowers and colleagues wrote.

In a 2021 report for the ASCO Educational Book, Dr. Flowers and hematologist-oncologist Demetria Smith-Graziani, MD, now with Emory University, explored disparities across blood cancers and barriers to minority enrollment in clinical trials. “Some approaches that clinicians can apply to address these disparities include increasing systems-level awareness, improving access to care, and reducing biases in clinical setting,” the authors wrote.

Luis Malpica Castillo, MD, assistant professor of lymphoma at MD Anderson Cancer Center, lauded the work of Dr. Flowers in expanding opportunities for minority patients with the disease.

“During the past years, Dr. Flowers’ work has not only had a positive impact on the Texan community, but minority populations living with cancer in the United States and abroad,” he said. “Currently, we are implementing cancer care networks aimed to increase diversity in clinical trials by enrolling a larger number of Hispanic and African American patients, who otherwise may not have benefited from novel therapies. The ultimate goal is to provide high-quality care to all patients living with cancer.”

In addition to his research work, Dr. Flowers is an advocate for diversity within the hematology community. He’s a founding member and former chair of the American Society of Hematology’s Committee on Diversity, Equity and Inclusion (formerly the Committee on Promoting Diversity), and he helped develop the society’s Minority Recruitment Initiative.

What’s next for Dr. Flowers? For one, he plans to continue working as a mentor; he received the ASH Mentor Award in honor of his service in 2022. “I am strongly committed to increasing the number of tenure-track investigators trained in clinical and translational cancer research and to promote their career development.”

And he looks forward to helping develop MD Anderson’s recently announced $2.5 billion hospital in Austin. “This will extend the exceptional care that we provide as the No. 1 cancer center in the United States,” he said. “It will also create new opportunities for research and collaboration with experts at UT Austin.”

When he’s not in clinic, Dr. Flowers embraces his lifelong love of speeding through life on his own two feet. He’s even inspired his children to share his passion. “I run most days of the week,” he said. “Running provides a great opportunity to think and process new research ideas, work through leadership challenges, and sometimes just to relax and let go of the day.”

Key clinical point: A low (below cutoff) geriatric nutritional risk index (GNRI) score is significantly associated with worse prognosis in patients with diffuse large B-cell lymphoma (DLBCL).

Major finding: A low GNRI score was significantly associated with worse overall survival (pooled hazard ratio [pHR] 1.78; P < .01) and progression-free survival (pHR 2.31; P < .01).

Study details: This meta-analysis included seven retrospective cohort studies that provided a cutoff value for GNRI (between 92 and 104.24) and involved 2448 patients with DLBCL for whom a calculated GNRI score was available.

Disclosures: This study was supported by Key R&D Projects, Jiangxi. The authors declared no conflicts of interest.

Source: Yan C et al. Prognostic value of geriatric nutritional risk index in patients with diffuse large B-cell lymphoma: A meta-analysis. Clin Transl Oncol. 2023 (Jul 12). doi: 10.1007/s12094-023-03271-w

Key clinical point: A low (below cutoff) geriatric nutritional risk index (GNRI) score is significantly associated with worse prognosis in patients with diffuse large B-cell lymphoma (DLBCL).

Major finding: A low GNRI score was significantly associated with worse overall survival (pooled hazard ratio [pHR] 1.78; P < .01) and progression-free survival (pHR 2.31; P < .01).

Study details: This meta-analysis included seven retrospective cohort studies that provided a cutoff value for GNRI (between 92 and 104.24) and involved 2448 patients with DLBCL for whom a calculated GNRI score was available.

Disclosures: This study was supported by Key R&D Projects, Jiangxi. The authors declared no conflicts of interest.

Source: Yan C et al. Prognostic value of geriatric nutritional risk index in patients with diffuse large B-cell lymphoma: A meta-analysis. Clin Transl Oncol. 2023 (Jul 12). doi: 10.1007/s12094-023-03271-w

Key clinical point: A low (below cutoff) geriatric nutritional risk index (GNRI) score is significantly associated with worse prognosis in patients with diffuse large B-cell lymphoma (DLBCL).

Major finding: A low GNRI score was significantly associated with worse overall survival (pooled hazard ratio [pHR] 1.78; P < .01) and progression-free survival (pHR 2.31; P < .01).

Study details: This meta-analysis included seven retrospective cohort studies that provided a cutoff value for GNRI (between 92 and 104.24) and involved 2448 patients with DLBCL for whom a calculated GNRI score was available.

Disclosures: This study was supported by Key R&D Projects, Jiangxi. The authors declared no conflicts of interest.

Source: Yan C et al. Prognostic value of geriatric nutritional risk index in patients with diffuse large B-cell lymphoma: A meta-analysis. Clin Transl Oncol. 2023 (Jul 12). doi: 10.1007/s12094-023-03271-w

Key clinical point: Serum levels of IL-6 and IL-10 at diagnosis may serve as predictors of treatment response and prognosis in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).

Major finding: Patients with partial or no rresponse vs complete response to treatment had significantly higher serum IL-6 (P = .009) and IL-10 (P < .001) levels. High serum IL-6 (≥ 4.5 pg/mL) and IL-10 (≥ 5.0 pg/mL) levels were independent prognostic factors for relapse (adjusted hazard ratio [aHR] 2.524; P = .003, and aHR 1.835; P = .007, respectively) and survival (aHR 2.012; P = .031, and aHR 5.312; P = .017, respectively).

Study details: This single-center retrospective study included 77 patients with newly diagnosed DLBCL and 77 matched control individuals without DLBCL.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Bao C et al. Cytokine profiles in patients with newly diagnosed diffuse large B-cell lymphoma: IL-6 and IL-10 levels are associated with adverse clinical features and poor outcomes. Cytokine. 2023;169:156289 (Jul 13). doi: 10.1016/j.cyto.2023.156289

Key clinical point: Serum levels of IL-6 and IL-10 at diagnosis may serve as predictors of treatment response and prognosis in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).

Major finding: Patients with partial or no rresponse vs complete response to treatment had significantly higher serum IL-6 (P = .009) and IL-10 (P < .001) levels. High serum IL-6 (≥ 4.5 pg/mL) and IL-10 (≥ 5.0 pg/mL) levels were independent prognostic factors for relapse (adjusted hazard ratio [aHR] 2.524; P = .003, and aHR 1.835; P = .007, respectively) and survival (aHR 2.012; P = .031, and aHR 5.312; P = .017, respectively).

Study details: This single-center retrospective study included 77 patients with newly diagnosed DLBCL and 77 matched control individuals without DLBCL.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Bao C et al. Cytokine profiles in patients with newly diagnosed diffuse large B-cell lymphoma: IL-6 and IL-10 levels are associated with adverse clinical features and poor outcomes. Cytokine. 2023;169:156289 (Jul 13). doi: 10.1016/j.cyto.2023.156289

Key clinical point: Serum levels of IL-6 and IL-10 at diagnosis may serve as predictors of treatment response and prognosis in patients with newly diagnosed diffuse large B-cell lymphoma (DLBCL).

Major finding: Patients with partial or no rresponse vs complete response to treatment had significantly higher serum IL-6 (P = .009) and IL-10 (P < .001) levels. High serum IL-6 (≥ 4.5 pg/mL) and IL-10 (≥ 5.0 pg/mL) levels were independent prognostic factors for relapse (adjusted hazard ratio [aHR] 2.524; P = .003, and aHR 1.835; P = .007, respectively) and survival (aHR 2.012; P = .031, and aHR 5.312; P = .017, respectively).

Study details: This single-center retrospective study included 77 patients with newly diagnosed DLBCL and 77 matched control individuals without DLBCL.

Disclosures: This study did not receive any funding. The authors declared no conflicts of interest.

Source: Bao C et al. Cytokine profiles in patients with newly diagnosed diffuse large B-cell lymphoma: IL-6 and IL-10 levels are associated with adverse clinical features and poor outcomes. Cytokine. 2023;169:156289 (Jul 13). doi: 10.1016/j.cyto.2023.156289

Key clinical point: Compared with rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP) or cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), bendamustine plus rituximab (BR) improved survival but led to increased hospital admissions for infections in patients with indolent B-cell lymphoma (BCL).

Major finding: Patients receiving BR vs R-CVP or R-CHOP had a significantly higher 5-year overall survival (80% vs 75%; adjusted hazard ratio 0.79; P < .01) but increased hospital admissions for infections during the first 9 months (21.9% vs 17.3%) and 36 months (41.2% vs 33.6%)  (both P < .01).

Study details: This retrospective real-world cohort study propensity-score matched patients with indolent BCL (mostly follicular lymphoma with other subtypes being marginal zone, lymphoplasmacytic, and small lymphocytic lymphoma, and hairy cell leukemia) who received BR (n = 2032) and those who received R-CVP or R-CHOP (n = 2032).

Disclosures: This study was funded by the Ontario Ministry of Health and the Ministry of Long-Term Care, Canada. The authors declared no conflicts of interest.

Source: Suleman A et al. Outcomes of patients with indolent lymphoma treated with bendamustine plus rituximab compared to rituximab plus CVP or CHOP chemoimmunotherapy in Ontario. Br J Haematol. 2023 (Jul 20). doi: 10.1111/bjh.18972

Key clinical point: Compared with rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP) or cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), bendamustine plus rituximab (BR) improved survival but led to increased hospital admissions for infections in patients with indolent B-cell lymphoma (BCL).

Major finding: Patients receiving BR vs R-CVP or R-CHOP had a significantly higher 5-year overall survival (80% vs 75%; adjusted hazard ratio 0.79; P < .01) but increased hospital admissions for infections during the first 9 months (21.9% vs 17.3%) and 36 months (41.2% vs 33.6%)  (both P < .01).

Study details: This retrospective real-world cohort study propensity-score matched patients with indolent BCL (mostly follicular lymphoma with other subtypes being marginal zone, lymphoplasmacytic, and small lymphocytic lymphoma, and hairy cell leukemia) who received BR (n = 2032) and those who received R-CVP or R-CHOP (n = 2032).

Disclosures: This study was funded by the Ontario Ministry of Health and the Ministry of Long-Term Care, Canada. The authors declared no conflicts of interest.

Source: Suleman A et al. Outcomes of patients with indolent lymphoma treated with bendamustine plus rituximab compared to rituximab plus CVP or CHOP chemoimmunotherapy in Ontario. Br J Haematol. 2023 (Jul 20). doi: 10.1111/bjh.18972

Key clinical point: Compared with rituximab plus cyclophosphamide, vincristine, and prednisone (R-CVP) or cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP), bendamustine plus rituximab (BR) improved survival but led to increased hospital admissions for infections in patients with indolent B-cell lymphoma (BCL).

Major finding: Patients receiving BR vs R-CVP or R-CHOP had a significantly higher 5-year overall survival (80% vs 75%; adjusted hazard ratio 0.79; P < .01) but increased hospital admissions for infections during the first 9 months (21.9% vs 17.3%) and 36 months (41.2% vs 33.6%)  (both P < .01).

Study details: This retrospective real-world cohort study propensity-score matched patients with indolent BCL (mostly follicular lymphoma with other subtypes being marginal zone, lymphoplasmacytic, and small lymphocytic lymphoma, and hairy cell leukemia) who received BR (n = 2032) and those who received R-CVP or R-CHOP (n = 2032).

Disclosures: This study was funded by the Ontario Ministry of Health and the Ministry of Long-Term Care, Canada. The authors declared no conflicts of interest.

Source: Suleman A et al. Outcomes of patients with indolent lymphoma treated with bendamustine plus rituximab compared to rituximab plus CVP or CHOP chemoimmunotherapy in Ontario. Br J Haematol. 2023 (Jul 20). doi: 10.1111/bjh.18972

Key clinical point: Lenalidomide combined with rituximab + etoposide, cytarabine, cisplatinum, and methylprednisolone (LR-ESHAP) shows promising efficacy and manageable toxicity and is a feasible salvage regimen before autologous stem-cell transplantation in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Major finding: The overall and complete response rates were 67% (95% CI 52%-81%) and 35% (95% CI 21%-50%), respectively. At a 41-month median follow-up, the median progression-free, overall, and event-free survival were 16 months (95% CI 4-28), 22 months (95% CI not estimable), and 7 months (95% CI 0-20), respectively. The most common grade ≥3 adverse events were thrombocytopenia (70%) and neutropenia (67%).

Study details: This phase 2 study included 46 adult patients with DLBCL who had relapsed after or were refractory to first-line therapy and received three cycles of LR-ESHAP.

Disclosures: This study was supported by the GELTAMO group (Spain) and Celgene Corporation. Some authors declared receiving consulting fees, research funding, travel support, or honoraria for lectures, presentations, or participation in speakers' bureaus or educational events from various sources, including Celgene. Fourteen authors declared no conflicts of interest.

Source: Martín García-Sancho A et al. Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: A phase 2 study from GELTAMO. Br J Haematol. 2023 (Jul 23). doi: 10.1111/bjh.18989

Key clinical point: Lenalidomide combined with rituximab + etoposide, cytarabine, cisplatinum, and methylprednisolone (LR-ESHAP) shows promising efficacy and manageable toxicity and is a feasible salvage regimen before autologous stem-cell transplantation in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Major finding: The overall and complete response rates were 67% (95% CI 52%-81%) and 35% (95% CI 21%-50%), respectively. At a 41-month median follow-up, the median progression-free, overall, and event-free survival were 16 months (95% CI 4-28), 22 months (95% CI not estimable), and 7 months (95% CI 0-20), respectively. The most common grade ≥3 adverse events were thrombocytopenia (70%) and neutropenia (67%).

Study details: This phase 2 study included 46 adult patients with DLBCL who had relapsed after or were refractory to first-line therapy and received three cycles of LR-ESHAP.

Disclosures: This study was supported by the GELTAMO group (Spain) and Celgene Corporation. Some authors declared receiving consulting fees, research funding, travel support, or honoraria for lectures, presentations, or participation in speakers' bureaus or educational events from various sources, including Celgene. Fourteen authors declared no conflicts of interest.

Source: Martín García-Sancho A et al. Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: A phase 2 study from GELTAMO. Br J Haematol. 2023 (Jul 23). doi: 10.1111/bjh.18989

Key clinical point: Lenalidomide combined with rituximab + etoposide, cytarabine, cisplatinum, and methylprednisolone (LR-ESHAP) shows promising efficacy and manageable toxicity and is a feasible salvage regimen before autologous stem-cell transplantation in patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL).

Major finding: The overall and complete response rates were 67% (95% CI 52%-81%) and 35% (95% CI 21%-50%), respectively. At a 41-month median follow-up, the median progression-free, overall, and event-free survival were 16 months (95% CI 4-28), 22 months (95% CI not estimable), and 7 months (95% CI 0-20), respectively. The most common grade ≥3 adverse events were thrombocytopenia (70%) and neutropenia (67%).

Study details: This phase 2 study included 46 adult patients with DLBCL who had relapsed after or were refractory to first-line therapy and received three cycles of LR-ESHAP.

Disclosures: This study was supported by the GELTAMO group (Spain) and Celgene Corporation. Some authors declared receiving consulting fees, research funding, travel support, or honoraria for lectures, presentations, or participation in speakers' bureaus or educational events from various sources, including Celgene. Fourteen authors declared no conflicts of interest.

Source: Martín García-Sancho A et al. Lenalidomide in combination with R-ESHAP in patients with relapsed or refractory diffuse large B-cell lymphoma: A phase 2 study from GELTAMO. Br J Haematol. 2023 (Jul 23). doi: 10.1111/bjh.18989

Key clinical point: Idelalisib demonstrated long-term efficacy in heavily pretreated patients with relapsed or refractory chronic lymphocytic leukemia (CLL), and despite having a relatively higher toxicity profile than other targeted therapeutics, can be used in such patients in the absence of alternative therapies.

Major finding: The overall response rate was 65%, with 1 patient achieving complete remission. At a median follow-up of 33.6 months, the median progression-free survival was 16.4 months (95% CI 10.4-26.3), whereas the median overall survival was not reached. Grade ≥ 3 adverse events occurred in 10 patients. The most common serious adverse event was grade ≥ 3 infection (65%).

Study details: This real-world observational retrospective study included 37 patients with CLL (for up to 2.5 years after idelalisib approval in 2014) who had relapsed after or were refractory to ≥ 1 prior lines of therapy and received idelalisib with or without concomitant rituximab.

Disclosures: This study was supported by grants from AFA Insurance (Australia), the Swedish Cancer Society, and others. Three authors declared receiving research grants or honoraria from various sources. The other authors did not have any conflicts of interest to disclose.

Source: Mattsson A et al. Idelalisib (PI3Kδ inhibitor) therapy for patients with relapsed/refractory chronic lymphocytic leukemia: A Swedish nation-wide real-world report on consecutively identified patients. Eur J Haematol. 2023 (Jul 27). doi: 10.1111/ejh.14065

Key clinical point: Idelalisib demonstrated long-term efficacy in heavily pretreated patients with relapsed or refractory chronic lymphocytic leukemia (CLL), and despite having a relatively higher toxicity profile than other targeted therapeutics, can be used in such patients in the absence of alternative therapies.

Major finding: The overall response rate was 65%, with 1 patient achieving complete remission. At a median follow-up of 33.6 months, the median progression-free survival was 16.4 months (95% CI 10.4-26.3), whereas the median overall survival was not reached. Grade ≥ 3 adverse events occurred in 10 patients. The most common serious adverse event was grade ≥ 3 infection (65%).

Study details: This real-world observational retrospective study included 37 patients with CLL (for up to 2.5 years after idelalisib approval in 2014) who had relapsed after or were refractory to ≥ 1 prior lines of therapy and received idelalisib with or without concomitant rituximab.

Disclosures: This study was supported by grants from AFA Insurance (Australia), the Swedish Cancer Society, and others. Three authors declared receiving research grants or honoraria from various sources. The other authors did not have any conflicts of interest to disclose.

Source: Mattsson A et al. Idelalisib (PI3Kδ inhibitor) therapy for patients with relapsed/refractory chronic lymphocytic leukemia: A Swedish nation-wide real-world report on consecutively identified patients. Eur J Haematol. 2023 (Jul 27). doi: 10.1111/ejh.14065

Key clinical point: Idelalisib demonstrated long-term efficacy in heavily pretreated patients with relapsed or refractory chronic lymphocytic leukemia (CLL), and despite having a relatively higher toxicity profile than other targeted therapeutics, can be used in such patients in the absence of alternative therapies.

Major finding: The overall response rate was 65%, with 1 patient achieving complete remission. At a median follow-up of 33.6 months, the median progression-free survival was 16.4 months (95% CI 10.4-26.3), whereas the median overall survival was not reached. Grade ≥ 3 adverse events occurred in 10 patients. The most common serious adverse event was grade ≥ 3 infection (65%).

Study details: This real-world observational retrospective study included 37 patients with CLL (for up to 2.5 years after idelalisib approval in 2014) who had relapsed after or were refractory to ≥ 1 prior lines of therapy and received idelalisib with or without concomitant rituximab.

Disclosures: This study was supported by grants from AFA Insurance (Australia), the Swedish Cancer Society, and others. Three authors declared receiving research grants or honoraria from various sources. The other authors did not have any conflicts of interest to disclose.

Source: Mattsson A et al. Idelalisib (PI3Kδ inhibitor) therapy for patients with relapsed/refractory chronic lymphocytic leukemia: A Swedish nation-wide real-world report on consecutively identified patients. Eur J Haematol. 2023 (Jul 27). doi: 10.1111/ejh.14065

Key clinical point: Compared with obinutuzumab alone, obinutuzumab combined with zanubrutinib significantly improved outcomes in patients with relapsed or refractory follicular lymphoma (FL) without causing safety concerns.

Major finding: At a median follow-up of 20.2 months, patients receiving zanubrutinib + obinutuzumab vs single-agent obinutuzumab had a significantly higher overall response rate (69% vs 46%; P = .001) and longer median progression-free survival (28.0 vs 10.4 months; hazard ratio 0.50; P < .001). The safety profile of zanubrutinib + obinutuzumab was consistent with the known safety profile of the individual drugs.

Study details: Findings are from the phase 2 ROSEWOOD study including 217 patients with FL who were refractory to or had relapsed after ≥ 2 prior systemic treatments, including an anti-CD20 antibody and alkylating agent, and were randomly assigned to receive zanubrutinib + obinutuzumab (n = 145) or Obinutuzumab alone (n = 72).

Disclosures: This study was sponsored by BeiGene. No information on conflicts of interest was provided.

Source: Zinzani PL et al. ROSEWOOD: A phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma. J Clin Oncol. 2023 (Jul 28). doi: 10.1200/JCO.23.00775

Key clinical point: Compared with obinutuzumab alone, obinutuzumab combined with zanubrutinib significantly improved outcomes in patients with relapsed or refractory follicular lymphoma (FL) without causing safety concerns.

Major finding: At a median follow-up of 20.2 months, patients receiving zanubrutinib + obinutuzumab vs single-agent obinutuzumab had a significantly higher overall response rate (69% vs 46%; P = .001) and longer median progression-free survival (28.0 vs 10.4 months; hazard ratio 0.50; P < .001). The safety profile of zanubrutinib + obinutuzumab was consistent with the known safety profile of the individual drugs.

Study details: Findings are from the phase 2 ROSEWOOD study including 217 patients with FL who were refractory to or had relapsed after ≥ 2 prior systemic treatments, including an anti-CD20 antibody and alkylating agent, and were randomly assigned to receive zanubrutinib + obinutuzumab (n = 145) or Obinutuzumab alone (n = 72).

Disclosures: This study was sponsored by BeiGene. No information on conflicts of interest was provided.

Source: Zinzani PL et al. ROSEWOOD: A phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma. J Clin Oncol. 2023 (Jul 28). doi: 10.1200/JCO.23.00775

Key clinical point: Compared with obinutuzumab alone, obinutuzumab combined with zanubrutinib significantly improved outcomes in patients with relapsed or refractory follicular lymphoma (FL) without causing safety concerns.

Major finding: At a median follow-up of 20.2 months, patients receiving zanubrutinib + obinutuzumab vs single-agent obinutuzumab had a significantly higher overall response rate (69% vs 46%; P = .001) and longer median progression-free survival (28.0 vs 10.4 months; hazard ratio 0.50; P < .001). The safety profile of zanubrutinib + obinutuzumab was consistent with the known safety profile of the individual drugs.

Study details: Findings are from the phase 2 ROSEWOOD study including 217 patients with FL who were refractory to or had relapsed after ≥ 2 prior systemic treatments, including an anti-CD20 antibody and alkylating agent, and were randomly assigned to receive zanubrutinib + obinutuzumab (n = 145) or Obinutuzumab alone (n = 72).

Disclosures: This study was sponsored by BeiGene. No information on conflicts of interest was provided.

Source: Zinzani PL et al. ROSEWOOD: A phase II randomized study of zanubrutinib plus obinutuzumab versus obinutuzumab monotherapy in patients with relapsed or refractory follicular lymphoma. J Clin Oncol. 2023 (Jul 28). doi: 10.1200/JCO.23.00775

Key clinical point: The addition of rituximab (R) to standard cyclophosphamide, doxorubicine, vincristine, and prednisone (CHOP) first-line therapy significantly prolongs failure-free survival (FFS), overall survival (OS), and the duration of response (DOR) in patients with previously untreated, advanced-stage mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 13.4 years, the R-CHOP vs CHOP group had significantly longer median FFS (2.07 vs 1.36 years; adjusted hazard ratio [aHR] 0.62; P < .0001), OS (5.81 vs 4.84 years; aHR 0.78; P = .039), and DOR (2.08 vs 1.48 years; aHR 0.67; P = .0012). No clinically meaningful differences in late toxicities were observed between the groups.

Study details: This long-term pooled trials analysis of two prospective randomized trials included 385 adult patients with untreated advanced-stage MCL who were randomly assigned to receive CHOP (n = 201) or R-CHOP (n = 184).

Disclosures: This study did not receive any specific funding. Some authors declared serving as advisors, consultants, or board members for or receiving research funding, travel support, or honoraria from various sources.

Source: Fischer L et al on behalf of the German Lymphoma Alliance (GLA) and the German Low-Grade Lymphoma Study Group (GLSG). The addition of rituximab to chemotherapy improves overall survival in mantle cell lymphoma-A pooled trials analysis. Ann Hematol. 2023 (Aug 8). doi: 10.1007/s00277-023-05385-1

Key clinical point: The addition of rituximab (R) to standard cyclophosphamide, doxorubicine, vincristine, and prednisone (CHOP) first-line therapy significantly prolongs failure-free survival (FFS), overall survival (OS), and the duration of response (DOR) in patients with previously untreated, advanced-stage mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 13.4 years, the R-CHOP vs CHOP group had significantly longer median FFS (2.07 vs 1.36 years; adjusted hazard ratio [aHR] 0.62; P < .0001), OS (5.81 vs 4.84 years; aHR 0.78; P = .039), and DOR (2.08 vs 1.48 years; aHR 0.67; P = .0012). No clinically meaningful differences in late toxicities were observed between the groups.

Study details: This long-term pooled trials analysis of two prospective randomized trials included 385 adult patients with untreated advanced-stage MCL who were randomly assigned to receive CHOP (n = 201) or R-CHOP (n = 184).

Disclosures: This study did not receive any specific funding. Some authors declared serving as advisors, consultants, or board members for or receiving research funding, travel support, or honoraria from various sources.

Source: Fischer L et al on behalf of the German Lymphoma Alliance (GLA) and the German Low-Grade Lymphoma Study Group (GLSG). The addition of rituximab to chemotherapy improves overall survival in mantle cell lymphoma-A pooled trials analysis. Ann Hematol. 2023 (Aug 8). doi: 10.1007/s00277-023-05385-1

Key clinical point: The addition of rituximab (R) to standard cyclophosphamide, doxorubicine, vincristine, and prednisone (CHOP) first-line therapy significantly prolongs failure-free survival (FFS), overall survival (OS), and the duration of response (DOR) in patients with previously untreated, advanced-stage mantle cell lymphoma (MCL).

Major finding: At a median follow-up of 13.4 years, the R-CHOP vs CHOP group had significantly longer median FFS (2.07 vs 1.36 years; adjusted hazard ratio [aHR] 0.62; P < .0001), OS (5.81 vs 4.84 years; aHR 0.78; P = .039), and DOR (2.08 vs 1.48 years; aHR 0.67; P = .0012). No clinically meaningful differences in late toxicities were observed between the groups.

Study details: This long-term pooled trials analysis of two prospective randomized trials included 385 adult patients with untreated advanced-stage MCL who were randomly assigned to receive CHOP (n = 201) or R-CHOP (n = 184).

Disclosures: This study did not receive any specific funding. Some authors declared serving as advisors, consultants, or board members for or receiving research funding, travel support, or honoraria from various sources.

Source: Fischer L et al on behalf of the German Lymphoma Alliance (GLA) and the German Low-Grade Lymphoma Study Group (GLSG). The addition of rituximab to chemotherapy improves overall survival in mantle cell lymphoma-A pooled trials analysis. Ann Hematol. 2023 (Aug 8). doi: 10.1007/s00277-023-05385-1