Hematologic Malignancies

Carfilzomib, a selective second-generation proteasome inhibitor, has performed well in clinical trials. So because other “triplets”—combinations of alkylator, proteasome inhibitor, and steroid—had shown “encouraging” response rates, researchers from the Center for Cancer and Blood Disorders in Bethesda, Maryland, and others, conducted a multicenter study to evaluate the safety and tolerability of twice-weekly carfilzomib combined with cyclophosphamide and dexamethasone (KCyd) for patients newly diagnosed with multiple myeloma (MM).

The researchers tested 3 doses of carfilzomib: 36 mg/m², 45 mg/m², and 56 mg/m². Of the 22 enrolled patients, 16 were treated with the maximum dose.

Fourteen patients completed all 8 cycles of treatment; 10 in the maximum-dose group completed all 8. At 56 mg/m², the overall response rate was 87.5%. Among the 14 patients whose disease responded to therapy, the median time to response was 1 month.

Five patients discontinued treatment because of adverse effects (AEs), but the researchers found no dose-limiting toxicities at any of the dose levels. The most common AEs were nausea, diarrhea, and anemia.

The researchers concluded that based on previous research, KCyd with 36 mg/m² is safe and effective in patients aged ≥ 65 years with newly diagnosed MM. However, their findings suggest that twice-weekly carfilzomib 56 mg/m² in combination with cyclophosphamide and dexamethasone also is effective with “manageable toxicity.”

Source:
Boccia RV, Bessudo A, Agajanian R, et al. Clin Lymphoma Myeloma Leuk. In press.
doi: 10.1016/j.clml.2017.05.009.

Carfilzomib, a selective second-generation proteasome inhibitor, has performed well in clinical trials. So because other “triplets”—combinations of alkylator, proteasome inhibitor, and steroid—had shown “encouraging” response rates, researchers from the Center for Cancer and Blood Disorders in Bethesda, Maryland, and others, conducted a multicenter study to evaluate the safety and tolerability of twice-weekly carfilzomib combined with cyclophosphamide and dexamethasone (KCyd) for patients newly diagnosed with multiple myeloma (MM).

The researchers tested 3 doses of carfilzomib: 36 mg/m², 45 mg/m², and 56 mg/m². Of the 22 enrolled patients, 16 were treated with the maximum dose.

Fourteen patients completed all 8 cycles of treatment; 10 in the maximum-dose group completed all 8. At 56 mg/m², the overall response rate was 87.5%. Among the 14 patients whose disease responded to therapy, the median time to response was 1 month.

Five patients discontinued treatment because of adverse effects (AEs), but the researchers found no dose-limiting toxicities at any of the dose levels. The most common AEs were nausea, diarrhea, and anemia.

The researchers concluded that based on previous research, KCyd with 36 mg/m² is safe and effective in patients aged ≥ 65 years with newly diagnosed MM. However, their findings suggest that twice-weekly carfilzomib 56 mg/m² in combination with cyclophosphamide and dexamethasone also is effective with “manageable toxicity.”

Source:
Boccia RV, Bessudo A, Agajanian R, et al. Clin Lymphoma Myeloma Leuk. In press.
doi: 10.1016/j.clml.2017.05.009.

Carfilzomib, a selective second-generation proteasome inhibitor, has performed well in clinical trials. So because other “triplets”—combinations of alkylator, proteasome inhibitor, and steroid—had shown “encouraging” response rates, researchers from the Center for Cancer and Blood Disorders in Bethesda, Maryland, and others, conducted a multicenter study to evaluate the safety and tolerability of twice-weekly carfilzomib combined with cyclophosphamide and dexamethasone (KCyd) for patients newly diagnosed with multiple myeloma (MM).

The researchers tested 3 doses of carfilzomib: 36 mg/m², 45 mg/m², and 56 mg/m². Of the 22 enrolled patients, 16 were treated with the maximum dose.

Fourteen patients completed all 8 cycles of treatment; 10 in the maximum-dose group completed all 8. At 56 mg/m², the overall response rate was 87.5%. Among the 14 patients whose disease responded to therapy, the median time to response was 1 month.

Five patients discontinued treatment because of adverse effects (AEs), but the researchers found no dose-limiting toxicities at any of the dose levels. The most common AEs were nausea, diarrhea, and anemia.

The researchers concluded that based on previous research, KCyd with 36 mg/m² is safe and effective in patients aged ≥ 65 years with newly diagnosed MM. However, their findings suggest that twice-weekly carfilzomib 56 mg/m² in combination with cyclophosphamide and dexamethasone also is effective with “manageable toxicity.”

Source:
Boccia RV, Bessudo A, Agajanian R, et al. Clin Lymphoma Myeloma Leuk. In press.
doi: 10.1016/j.clml.2017.05.009.

As more people are surviving breast cancer, more will be given bisphosphonate (BP) for bone metastases—and may be at risk for treatment adverse effects, such as atypical femoral fracture (AFF). Clinicians from Royal Victoria Hospital, Belfast, United Kingdom, describe what they learned in the first reported case of AFF caused by daily ibandronate.

The patient, a 55-year-old woman, had been diagnosed and treated for breast cancer. Twelve years later, she began having hip and lower back pain and was diagnosed with bony metastatic spread. She was started on hormone-suppressing therapy as well as daily ibandronic acid. Four years later, she began having new lower limb and groin pain. Radiography, bone scans and other tests indicated further metastatic spread to her left femur.

While she was waiting for scheduled radiotherapy, she fell, fracturing her left femur. Radiographs revealed AFF, presumed secondary to her BP therapy rather than metastasis. She underwent intramedullary nail fixation.

Evidence suggests that AFFs are stress fractures, the clinicians say. Repetitive loading on bone can lead to micro cracks, which are even more vulnerable to stress when BPs suppress the normal bone repair process.

Atypical femoral fracture is rare. Most cases have been patients receiving intravenous BP; to the clinicians’ knowledge this is the first report of AFF with an oral BP prescribed for bone metastatic breast cancer. But incidence of AFF grows with prolonged treatment, and the risk is raised with oral dosing, which is much higher in cancer cases, the clinicians note, compared with osteoporosis.

Because patients often have prodromal pain before an overt break, the clinicians suggest asking all oncology patients on BP about pain in thigh, hip, or groin. Bone scans and magnetic resonance imaging may reveal an imminent fracture. The clinicians caution that AFFs can be bilateral, so the opposite side also should be imaged.

Source:

Espey R, Grimes S, Heyburn G, Kealey WD. BMJ Case Rep. 2017;2017. pii: bcr-2016-217489.
doi: 10.1136/bcr-2016-217489.

As more people are surviving breast cancer, more will be given bisphosphonate (BP) for bone metastases—and may be at risk for treatment adverse effects, such as atypical femoral fracture (AFF). Clinicians from Royal Victoria Hospital, Belfast, United Kingdom, describe what they learned in the first reported case of AFF caused by daily ibandronate.

The patient, a 55-year-old woman, had been diagnosed and treated for breast cancer. Twelve years later, she began having hip and lower back pain and was diagnosed with bony metastatic spread. She was started on hormone-suppressing therapy as well as daily ibandronic acid. Four years later, she began having new lower limb and groin pain. Radiography, bone scans and other tests indicated further metastatic spread to her left femur.

While she was waiting for scheduled radiotherapy, she fell, fracturing her left femur. Radiographs revealed AFF, presumed secondary to her BP therapy rather than metastasis. She underwent intramedullary nail fixation.

Evidence suggests that AFFs are stress fractures, the clinicians say. Repetitive loading on bone can lead to micro cracks, which are even more vulnerable to stress when BPs suppress the normal bone repair process.

Atypical femoral fracture is rare. Most cases have been patients receiving intravenous BP; to the clinicians’ knowledge this is the first report of AFF with an oral BP prescribed for bone metastatic breast cancer. But incidence of AFF grows with prolonged treatment, and the risk is raised with oral dosing, which is much higher in cancer cases, the clinicians note, compared with osteoporosis.

Because patients often have prodromal pain before an overt break, the clinicians suggest asking all oncology patients on BP about pain in thigh, hip, or groin. Bone scans and magnetic resonance imaging may reveal an imminent fracture. The clinicians caution that AFFs can be bilateral, so the opposite side also should be imaged.

Source:

Espey R, Grimes S, Heyburn G, Kealey WD. BMJ Case Rep. 2017;2017. pii: bcr-2016-217489.
doi: 10.1136/bcr-2016-217489.

As more people are surviving breast cancer, more will be given bisphosphonate (BP) for bone metastases—and may be at risk for treatment adverse effects, such as atypical femoral fracture (AFF). Clinicians from Royal Victoria Hospital, Belfast, United Kingdom, describe what they learned in the first reported case of AFF caused by daily ibandronate.

The patient, a 55-year-old woman, had been diagnosed and treated for breast cancer. Twelve years later, she began having hip and lower back pain and was diagnosed with bony metastatic spread. She was started on hormone-suppressing therapy as well as daily ibandronic acid. Four years later, she began having new lower limb and groin pain. Radiography, bone scans and other tests indicated further metastatic spread to her left femur.

While she was waiting for scheduled radiotherapy, she fell, fracturing her left femur. Radiographs revealed AFF, presumed secondary to her BP therapy rather than metastasis. She underwent intramedullary nail fixation.

Evidence suggests that AFFs are stress fractures, the clinicians say. Repetitive loading on bone can lead to micro cracks, which are even more vulnerable to stress when BPs suppress the normal bone repair process.

Atypical femoral fracture is rare. Most cases have been patients receiving intravenous BP; to the clinicians’ knowledge this is the first report of AFF with an oral BP prescribed for bone metastatic breast cancer. But incidence of AFF grows with prolonged treatment, and the risk is raised with oral dosing, which is much higher in cancer cases, the clinicians note, compared with osteoporosis.

Because patients often have prodromal pain before an overt break, the clinicians suggest asking all oncology patients on BP about pain in thigh, hip, or groin. Bone scans and magnetic resonance imaging may reveal an imminent fracture. The clinicians caution that AFFs can be bilateral, so the opposite side also should be imaged.

Source:

Espey R, Grimes S, Heyburn G, Kealey WD. BMJ Case Rep. 2017;2017. pii: bcr-2016-217489.
doi: 10.1136/bcr-2016-217489.

MADRID – The evidence thus far comes only from animal models, but commonly encountered childhood infections may be able to trigger the development of leukemia in those children with certain genetic predispositions to B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Mice genetically modified to mimic BCP-ALL susceptibility and its most common subtype (ETV6-RUNX1 BCP-ALL) developed leukemia only after exposure to a common infectious environment.

[email protected]

MADRID – The evidence thus far comes only from animal models, but commonly encountered childhood infections may be able to trigger the development of leukemia in those children with certain genetic predispositions to B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Mice genetically modified to mimic BCP-ALL susceptibility and its most common subtype (ETV6-RUNX1 BCP-ALL) developed leukemia only after exposure to a common infectious environment.

[email protected]

MADRID – The evidence thus far comes only from animal models, but commonly encountered childhood infections may be able to trigger the development of leukemia in those children with certain genetic predispositions to B-cell precursor acute lymphoblastic leukemia (BCP-ALL).

Mice genetically modified to mimic BCP-ALL susceptibility and its most common subtype (ETV6-RUNX1 BCP-ALL) developed leukemia only after exposure to a common infectious environment.

[email protected]

Lugano, Switzerland – It’s not the end of chemotherapy for young patients with newly diagnosed mantle cell lymphoma (MCL), but it’s a start.

For these patients, induction with a combination of ibrutinib and rituximab, followed by shorter cycles of chemoimmunotherapy, was associated in an early study with an objective response rate of 100%, including 90% complete responses (CR), reported Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This is the first time for a chemo-free therapy – ibrutinib/rituximab – to achieve an overall response rate of 100%. This has an unprecedented efficacy in the frontline in young patients with mantle-cell lymphoma,” he said at the 14th International Congress on Malignant Lymphoma.

In patients with relapsed or refractory MCL, the combination of ibrutinib and rituximab has been associated with durable responses in 88% of patients. The success of the combination suggests that fit patients younger than age 65 years with newly diagnosed MCL might benefit from a chemotherapy-free induction regimen with ibrutinib and rituximab, followed by consolidation with a short but intense course of chemoimmunotherapy, Dr. Wang said.

He presented updated results from the phase II Window I study, first results of which were reported at the 2016 meeting of the American Society of Hematology.

“Frontline therapy is the most important therapy for mantle cell lymphoma, because mantle cell lymphoma cells are most vulnerable to frontline attack. If the frontline therapy is good enough, it could kill all the mantle cell lymphoma cells, therefore leaving no chance for secondary resistance, and thereby (resulting in) long-term survival. And it is really my belief that if we ideally optimized the frontline therapy, that would be a shortcut to a cure,” he said.

To test this idea, Dr. Wang and MD Anderson colleagues initiated a phase II trial at their institution with 50 patients age 65 years or under with newly diagnosed, CD20-positive and Cyclin D1-positive MCL.

A total of 50 patients age 65 years or younger (median age 54) with newly diagnosed, untreated MCL underwent induction with continuous daily ibrutinib 560 mg, plus rituximab 375 mg/m² administered weekly for 4 weeks during cycle 1 and on day 1 of cycles 3-12. Consolidation consisted of rituximab plus hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), alternating every 28 days with rituximab plus high-dose methotrexate–cytarabine.

Patients who had complete responses to induction received four cycles of chemoimmunotherapy, while those who experienced disease progression and those who had partial responses received chemoimmunotherapy for two cycles beyond the point of complete remissions.

At the time of the presentation, all 50 patients were evaluable for the induction phase (part 2), and 47 were evaluable for both induction and consolidation (part 2) .Of the evaluable patients, the overall response rate (ORR) to chemotherapy-free induction therapy alone (Part 1 ) was 100% (50), with CR in 90% of patients and partial responses (PR) in 10%. Of the 47 patients evaluable for part 2 (chemoimmunotherapy), all had CRs, for an ORR of 100%.

Dr. Wang noted that one patient had a dramatic radiographic reduction in spleen size following just two cycles of chemotherapy-free induction, and two other patients had similar reductions after four and six cycles, respectively.

After a median follow-up of 15.9 months, neither the median duration of response, progression-free survival, nor overall survival have been reached. There have been no deaths and only one case of disease progression after one year of therapy.

The patients generally tolerated the regimen very well, Dr. Wang said. There were no cases of lymphocytosis, bleeding, or atrial fibrillation after 332 combined cycles.

Nonhematological adverse events were primarily grade 1 or 2. Grade 3 fatigue was reported in approximately 10% of patients. There were no grade 4 adverse events.

“This study may provide a window of opportunity to reduce the frontline therapies and reduce the long-term toxicities such as secondary malignancies.” Dr. Wang said.

He acknowledged that four cycles of intensive chemotherapy is still toxic and that further efforts to reduce these toxicities are needed. The investigators are currently planning the Window II study, in which a fraction of patients will be treated with no chemotherapy at all, he said.­­­­

The study was supported by Pharmacyclics and Janssen. Dr. Wang disclosed receiving research grants and honoraria and serving as a consultant for the companies.

Lugano, Switzerland – It’s not the end of chemotherapy for young patients with newly diagnosed mantle cell lymphoma (MCL), but it’s a start.

For these patients, induction with a combination of ibrutinib and rituximab, followed by shorter cycles of chemoimmunotherapy, was associated in an early study with an objective response rate of 100%, including 90% complete responses (CR), reported Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This is the first time for a chemo-free therapy – ibrutinib/rituximab – to achieve an overall response rate of 100%. This has an unprecedented efficacy in the frontline in young patients with mantle-cell lymphoma,” he said at the 14th International Congress on Malignant Lymphoma.

In patients with relapsed or refractory MCL, the combination of ibrutinib and rituximab has been associated with durable responses in 88% of patients. The success of the combination suggests that fit patients younger than age 65 years with newly diagnosed MCL might benefit from a chemotherapy-free induction regimen with ibrutinib and rituximab, followed by consolidation with a short but intense course of chemoimmunotherapy, Dr. Wang said.

He presented updated results from the phase II Window I study, first results of which were reported at the 2016 meeting of the American Society of Hematology.

“Frontline therapy is the most important therapy for mantle cell lymphoma, because mantle cell lymphoma cells are most vulnerable to frontline attack. If the frontline therapy is good enough, it could kill all the mantle cell lymphoma cells, therefore leaving no chance for secondary resistance, and thereby (resulting in) long-term survival. And it is really my belief that if we ideally optimized the frontline therapy, that would be a shortcut to a cure,” he said.

To test this idea, Dr. Wang and MD Anderson colleagues initiated a phase II trial at their institution with 50 patients age 65 years or under with newly diagnosed, CD20-positive and Cyclin D1-positive MCL.

A total of 50 patients age 65 years or younger (median age 54) with newly diagnosed, untreated MCL underwent induction with continuous daily ibrutinib 560 mg, plus rituximab 375 mg/m² administered weekly for 4 weeks during cycle 1 and on day 1 of cycles 3-12. Consolidation consisted of rituximab plus hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), alternating every 28 days with rituximab plus high-dose methotrexate–cytarabine.

Patients who had complete responses to induction received four cycles of chemoimmunotherapy, while those who experienced disease progression and those who had partial responses received chemoimmunotherapy for two cycles beyond the point of complete remissions.

At the time of the presentation, all 50 patients were evaluable for the induction phase (part 2), and 47 were evaluable for both induction and consolidation (part 2) .Of the evaluable patients, the overall response rate (ORR) to chemotherapy-free induction therapy alone (Part 1 ) was 100% (50), with CR in 90% of patients and partial responses (PR) in 10%. Of the 47 patients evaluable for part 2 (chemoimmunotherapy), all had CRs, for an ORR of 100%.

Dr. Wang noted that one patient had a dramatic radiographic reduction in spleen size following just two cycles of chemotherapy-free induction, and two other patients had similar reductions after four and six cycles, respectively.

After a median follow-up of 15.9 months, neither the median duration of response, progression-free survival, nor overall survival have been reached. There have been no deaths and only one case of disease progression after one year of therapy.

The patients generally tolerated the regimen very well, Dr. Wang said. There were no cases of lymphocytosis, bleeding, or atrial fibrillation after 332 combined cycles.

Nonhematological adverse events were primarily grade 1 or 2. Grade 3 fatigue was reported in approximately 10% of patients. There were no grade 4 adverse events.

“This study may provide a window of opportunity to reduce the frontline therapies and reduce the long-term toxicities such as secondary malignancies.” Dr. Wang said.

He acknowledged that four cycles of intensive chemotherapy is still toxic and that further efforts to reduce these toxicities are needed. The investigators are currently planning the Window II study, in which a fraction of patients will be treated with no chemotherapy at all, he said.­­­­

The study was supported by Pharmacyclics and Janssen. Dr. Wang disclosed receiving research grants and honoraria and serving as a consultant for the companies.

Lugano, Switzerland – It’s not the end of chemotherapy for young patients with newly diagnosed mantle cell lymphoma (MCL), but it’s a start.

For these patients, induction with a combination of ibrutinib and rituximab, followed by shorter cycles of chemoimmunotherapy, was associated in an early study with an objective response rate of 100%, including 90% complete responses (CR), reported Michael Wang, MD, of the University of Texas MD Anderson Cancer Center in Houston.

“This is the first time for a chemo-free therapy – ibrutinib/rituximab – to achieve an overall response rate of 100%. This has an unprecedented efficacy in the frontline in young patients with mantle-cell lymphoma,” he said at the 14th International Congress on Malignant Lymphoma.

In patients with relapsed or refractory MCL, the combination of ibrutinib and rituximab has been associated with durable responses in 88% of patients. The success of the combination suggests that fit patients younger than age 65 years with newly diagnosed MCL might benefit from a chemotherapy-free induction regimen with ibrutinib and rituximab, followed by consolidation with a short but intense course of chemoimmunotherapy, Dr. Wang said.

He presented updated results from the phase II Window I study, first results of which were reported at the 2016 meeting of the American Society of Hematology.

“Frontline therapy is the most important therapy for mantle cell lymphoma, because mantle cell lymphoma cells are most vulnerable to frontline attack. If the frontline therapy is good enough, it could kill all the mantle cell lymphoma cells, therefore leaving no chance for secondary resistance, and thereby (resulting in) long-term survival. And it is really my belief that if we ideally optimized the frontline therapy, that would be a shortcut to a cure,” he said.

To test this idea, Dr. Wang and MD Anderson colleagues initiated a phase II trial at their institution with 50 patients age 65 years or under with newly diagnosed, CD20-positive and Cyclin D1-positive MCL.

A total of 50 patients age 65 years or younger (median age 54) with newly diagnosed, untreated MCL underwent induction with continuous daily ibrutinib 560 mg, plus rituximab 375 mg/m² administered weekly for 4 weeks during cycle 1 and on day 1 of cycles 3-12. Consolidation consisted of rituximab plus hyper-CVAD (hyper-fractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone), alternating every 28 days with rituximab plus high-dose methotrexate–cytarabine.

Patients who had complete responses to induction received four cycles of chemoimmunotherapy, while those who experienced disease progression and those who had partial responses received chemoimmunotherapy for two cycles beyond the point of complete remissions.

At the time of the presentation, all 50 patients were evaluable for the induction phase (part 2), and 47 were evaluable for both induction and consolidation (part 2) .Of the evaluable patients, the overall response rate (ORR) to chemotherapy-free induction therapy alone (Part 1 ) was 100% (50), with CR in 90% of patients and partial responses (PR) in 10%. Of the 47 patients evaluable for part 2 (chemoimmunotherapy), all had CRs, for an ORR of 100%.

Dr. Wang noted that one patient had a dramatic radiographic reduction in spleen size following just two cycles of chemotherapy-free induction, and two other patients had similar reductions after four and six cycles, respectively.

After a median follow-up of 15.9 months, neither the median duration of response, progression-free survival, nor overall survival have been reached. There have been no deaths and only one case of disease progression after one year of therapy.

The patients generally tolerated the regimen very well, Dr. Wang said. There were no cases of lymphocytosis, bleeding, or atrial fibrillation after 332 combined cycles.

Nonhematological adverse events were primarily grade 1 or 2. Grade 3 fatigue was reported in approximately 10% of patients. There were no grade 4 adverse events.

“This study may provide a window of opportunity to reduce the frontline therapies and reduce the long-term toxicities such as secondary malignancies.” Dr. Wang said.

He acknowledged that four cycles of intensive chemotherapy is still toxic and that further efforts to reduce these toxicities are needed. The investigators are currently planning the Window II study, in which a fraction of patients will be treated with no chemotherapy at all, he said.­­­­

The study was supported by Pharmacyclics and Janssen. Dr. Wang disclosed receiving research grants and honoraria and serving as a consultant for the companies.

Lugano, Switzerland– It’s in the BAG: For patients with treatment-naive or relapsed/refractory chronic lymphocytic leukemia, a regimen consisting of debulking with bendamustine (Treanda) followed sequentially by obinutuzumab (Gazyva) and venetoclax (Venclexta) was associated with a high overall response rate and a large majority of patients being negative for minimal residual disease (MRD) in peripheral blood.

In the open-label, phase II CLL2-BAG study in 66 patients, the overall response rate at the end of induction was 95%, and 87% of patients were negative for MRD, reported Paula Cramer, MD, of the University of Cologne (Germany).

“This sequential treatment of bendamustine followed by obinutuzumab and venetoclax does not lead to any cumulative or unexpected toxicity. As compared to other trials, it’s important to point out that only one laboratory TLS [tumor lysis syndrome] occurred with venetoclax. Maybe that’s explained by the sequential start of all three drugs,” she said at the International Conference on Malignant Lymphoma.

The trial is based on a concept the investigators call “sequential triple-T” (tailored and targeted treatment) aimed at complete eradication of MRD.

The 66 patients (median age, 59 years) had either previously untreated or relapsed/refractory CLL; 34 of the treatment-naive and 29 of the relapsed/refractory patients were evaluable for response.

At enrollment, patients who had an absolute lymphocyte count of 25,000/mcL or greater and/or lymph nodes 5 cm or larger received two cycles of debulking with bendamustine 70 mg/m² on days 1 and 2 every 28 days, unless this was contraindicated.

The induction phase consisted of obinutuzumab 1,000 mg administered three times in cycle 1, then every 4 weeks for cycles 2 through 6. Venetoclax was started during cycle 2 with a dose escalation to 400 mg daily over a period of 5 weeks.

Maintenance therapy consisted of daily venetoclax and obinutuzumab every 3 months until MRD negativity or up to 24 months.

A total of 45 patients (31 who were treatment naive and 14 with relapsed/refractory disease) underwent debulking. Of this group 36 patients received both cycles, and 9 discontinued early because of either adverse events (5 patients), disease progression (1), or unknown reasons (3).

Sixty of the 66 patients received the full six induction cycles. Three patients who had fewer than two cycles were excluded according to protocol. Of these three, two heavily pretreated patients died of sepsis and one of myocardial infarction in cycle 1.

Responses

In all, 24 patients (53%) who had debulking had a response during that phase based on International Workshop on CLL (IWCLL) criteria, for an overall response rate (ORR) of 53%. Thirteen patients had stable disease after debulking, and four had disease progression.

Responses after induction according to IWCLL criteria, the primary endpoint, included five patients with a complete response (three treatment-naive and two relapsed/refractory patients), and 20 patients (14 treatment-naive and six relapsed/refractory patients) with an unconfirmed or clinical complete response or a complete response with incomplete recovery of counts.

In addition, 35 patients (17 who were treatment naive and 18 with relapsed/refractory disease) had a partial response. No patients had stable disease, and three patients, all with relapsed/refractory disease, had disease progression.

Of the 63 patients who had at least two cycles of therapy, 87% were MRD negative. Eight patients had MRD assessments by bone marrow, and all eight were MRD negative.

The maintenance phase of the trial is ongoing and the data are not mature, but 56 patients (30 who were treatment naive and 26 with relapsed/refractory disease) have started on maintenance therapy. Of this group, 28 have stopped maintenance, including 21 patients who stopped because they achieved MRD negativity, 5 who discontinued because of adverse events, and 2 with disease progression or Richter’s transformation.

At 15 months of follow-up, progression-free survival was 100% in patients who received the combination as the frontline therapy, and 83% in the patients with relapsed/refractory disease.

Adverse events

In the debulking phase, 34 patients (72%) experienced adverse events of any grade, including 16 patients with grade 3 or 4 events

Adverse events associated with debulking included neutropenia and anemia, each seen in five patients, thrombocytopenia and infection each seen in three patients, and coronary artery disorders, rash, tumor lysis syndrome, vomiting, and pyrexia in one patient each.

Sixty of the 66 patients received the full six induction cycles. Three patients who had fewer than two cycles were excluded according to protocol. Of these three, two heavily pretreated patients died of sepsis and one of myocardial infarction in cycle 1.

All but 3 of the 63 patients had an adverse event, and 44 patients had at least one grade 3 or 4 adverse event.

Cytopenias, infections, infusion-related reactions, and neoplasms were the most common adverse events.

There were three grade 3 laboratory-confirmed cases of tumor lysis syndrome, one each occurring during bendamustine debulking, obinutuzumab administration, and venetoclax administration.

Something other than venetoclax?

Davide Rossi, MD, PhD, of the Oncology Institute of Southern Switzerland in Bellinzona, the invited discussant, questioned whether venetoclax is the best agent to use in sequential triple-T therapy.

“We know that venetoclax is more active in blood and bone marrow than in lymph nodes and, indeed, a proportion of cases achieving all the criteria for a CR [complete response] in the bone marrow and the peripheral blood, including MRD negativity, may still have some residual [disease in] lymph nodes,” he said.

Drugs that inhibit the B-cell receptor pathway may be more effective at eradicating MRD in the lymph node compartment, Dr. Cramer said.

The study was sponsored by the German CLL study group. Dr. Cramer disclosed financial ties to multiple entities. Dr. Rossi did not report disclosures.
 

Lugano, Switzerland– It’s in the BAG: For patients with treatment-naive or relapsed/refractory chronic lymphocytic leukemia, a regimen consisting of debulking with bendamustine (Treanda) followed sequentially by obinutuzumab (Gazyva) and venetoclax (Venclexta) was associated with a high overall response rate and a large majority of patients being negative for minimal residual disease (MRD) in peripheral blood.

In the open-label, phase II CLL2-BAG study in 66 patients, the overall response rate at the end of induction was 95%, and 87% of patients were negative for MRD, reported Paula Cramer, MD, of the University of Cologne (Germany).

“This sequential treatment of bendamustine followed by obinutuzumab and venetoclax does not lead to any cumulative or unexpected toxicity. As compared to other trials, it’s important to point out that only one laboratory TLS [tumor lysis syndrome] occurred with venetoclax. Maybe that’s explained by the sequential start of all three drugs,” she said at the International Conference on Malignant Lymphoma.

The trial is based on a concept the investigators call “sequential triple-T” (tailored and targeted treatment) aimed at complete eradication of MRD.

The 66 patients (median age, 59 years) had either previously untreated or relapsed/refractory CLL; 34 of the treatment-naive and 29 of the relapsed/refractory patients were evaluable for response.

At enrollment, patients who had an absolute lymphocyte count of 25,000/mcL or greater and/or lymph nodes 5 cm or larger received two cycles of debulking with bendamustine 70 mg/m² on days 1 and 2 every 28 days, unless this was contraindicated.

The induction phase consisted of obinutuzumab 1,000 mg administered three times in cycle 1, then every 4 weeks for cycles 2 through 6. Venetoclax was started during cycle 2 with a dose escalation to 400 mg daily over a period of 5 weeks.

Maintenance therapy consisted of daily venetoclax and obinutuzumab every 3 months until MRD negativity or up to 24 months.

A total of 45 patients (31 who were treatment naive and 14 with relapsed/refractory disease) underwent debulking. Of this group 36 patients received both cycles, and 9 discontinued early because of either adverse events (5 patients), disease progression (1), or unknown reasons (3).

Sixty of the 66 patients received the full six induction cycles. Three patients who had fewer than two cycles were excluded according to protocol. Of these three, two heavily pretreated patients died of sepsis and one of myocardial infarction in cycle 1.

Responses

In all, 24 patients (53%) who had debulking had a response during that phase based on International Workshop on CLL (IWCLL) criteria, for an overall response rate (ORR) of 53%. Thirteen patients had stable disease after debulking, and four had disease progression.

Responses after induction according to IWCLL criteria, the primary endpoint, included five patients with a complete response (three treatment-naive and two relapsed/refractory patients), and 20 patients (14 treatment-naive and six relapsed/refractory patients) with an unconfirmed or clinical complete response or a complete response with incomplete recovery of counts.

In addition, 35 patients (17 who were treatment naive and 18 with relapsed/refractory disease) had a partial response. No patients had stable disease, and three patients, all with relapsed/refractory disease, had disease progression.

Of the 63 patients who had at least two cycles of therapy, 87% were MRD negative. Eight patients had MRD assessments by bone marrow, and all eight were MRD negative.

The maintenance phase of the trial is ongoing and the data are not mature, but 56 patients (30 who were treatment naive and 26 with relapsed/refractory disease) have started on maintenance therapy. Of this group, 28 have stopped maintenance, including 21 patients who stopped because they achieved MRD negativity, 5 who discontinued because of adverse events, and 2 with disease progression or Richter’s transformation.

At 15 months of follow-up, progression-free survival was 100% in patients who received the combination as the frontline therapy, and 83% in the patients with relapsed/refractory disease.

Adverse events

In the debulking phase, 34 patients (72%) experienced adverse events of any grade, including 16 patients with grade 3 or 4 events

Adverse events associated with debulking included neutropenia and anemia, each seen in five patients, thrombocytopenia and infection each seen in three patients, and coronary artery disorders, rash, tumor lysis syndrome, vomiting, and pyrexia in one patient each.

Sixty of the 66 patients received the full six induction cycles. Three patients who had fewer than two cycles were excluded according to protocol. Of these three, two heavily pretreated patients died of sepsis and one of myocardial infarction in cycle 1.

All but 3 of the 63 patients had an adverse event, and 44 patients had at least one grade 3 or 4 adverse event.

Cytopenias, infections, infusion-related reactions, and neoplasms were the most common adverse events.

There were three grade 3 laboratory-confirmed cases of tumor lysis syndrome, one each occurring during bendamustine debulking, obinutuzumab administration, and venetoclax administration.

Something other than venetoclax?

Davide Rossi, MD, PhD, of the Oncology Institute of Southern Switzerland in Bellinzona, the invited discussant, questioned whether venetoclax is the best agent to use in sequential triple-T therapy.

“We know that venetoclax is more active in blood and bone marrow than in lymph nodes and, indeed, a proportion of cases achieving all the criteria for a CR [complete response] in the bone marrow and the peripheral blood, including MRD negativity, may still have some residual [disease in] lymph nodes,” he said.

Drugs that inhibit the B-cell receptor pathway may be more effective at eradicating MRD in the lymph node compartment, Dr. Cramer said.

The study was sponsored by the German CLL study group. Dr. Cramer disclosed financial ties to multiple entities. Dr. Rossi did not report disclosures.
 

Lugano, Switzerland– It’s in the BAG: For patients with treatment-naive or relapsed/refractory chronic lymphocytic leukemia, a regimen consisting of debulking with bendamustine (Treanda) followed sequentially by obinutuzumab (Gazyva) and venetoclax (Venclexta) was associated with a high overall response rate and a large majority of patients being negative for minimal residual disease (MRD) in peripheral blood.

In the open-label, phase II CLL2-BAG study in 66 patients, the overall response rate at the end of induction was 95%, and 87% of patients were negative for MRD, reported Paula Cramer, MD, of the University of Cologne (Germany).

“This sequential treatment of bendamustine followed by obinutuzumab and venetoclax does not lead to any cumulative or unexpected toxicity. As compared to other trials, it’s important to point out that only one laboratory TLS [tumor lysis syndrome] occurred with venetoclax. Maybe that’s explained by the sequential start of all three drugs,” she said at the International Conference on Malignant Lymphoma.

The trial is based on a concept the investigators call “sequential triple-T” (tailored and targeted treatment) aimed at complete eradication of MRD.

The 66 patients (median age, 59 years) had either previously untreated or relapsed/refractory CLL; 34 of the treatment-naive and 29 of the relapsed/refractory patients were evaluable for response.

At enrollment, patients who had an absolute lymphocyte count of 25,000/mcL or greater and/or lymph nodes 5 cm or larger received two cycles of debulking with bendamustine 70 mg/m² on days 1 and 2 every 28 days, unless this was contraindicated.

The induction phase consisted of obinutuzumab 1,000 mg administered three times in cycle 1, then every 4 weeks for cycles 2 through 6. Venetoclax was started during cycle 2 with a dose escalation to 400 mg daily over a period of 5 weeks.

Maintenance therapy consisted of daily venetoclax and obinutuzumab every 3 months until MRD negativity or up to 24 months.

A total of 45 patients (31 who were treatment naive and 14 with relapsed/refractory disease) underwent debulking. Of this group 36 patients received both cycles, and 9 discontinued early because of either adverse events (5 patients), disease progression (1), or unknown reasons (3).

Sixty of the 66 patients received the full six induction cycles. Three patients who had fewer than two cycles were excluded according to protocol. Of these three, two heavily pretreated patients died of sepsis and one of myocardial infarction in cycle 1.

Responses

In all, 24 patients (53%) who had debulking had a response during that phase based on International Workshop on CLL (IWCLL) criteria, for an overall response rate (ORR) of 53%. Thirteen patients had stable disease after debulking, and four had disease progression.

Responses after induction according to IWCLL criteria, the primary endpoint, included five patients with a complete response (three treatment-naive and two relapsed/refractory patients), and 20 patients (14 treatment-naive and six relapsed/refractory patients) with an unconfirmed or clinical complete response or a complete response with incomplete recovery of counts.

In addition, 35 patients (17 who were treatment naive and 18 with relapsed/refractory disease) had a partial response. No patients had stable disease, and three patients, all with relapsed/refractory disease, had disease progression.

Of the 63 patients who had at least two cycles of therapy, 87% were MRD negative. Eight patients had MRD assessments by bone marrow, and all eight were MRD negative.

The maintenance phase of the trial is ongoing and the data are not mature, but 56 patients (30 who were treatment naive and 26 with relapsed/refractory disease) have started on maintenance therapy. Of this group, 28 have stopped maintenance, including 21 patients who stopped because they achieved MRD negativity, 5 who discontinued because of adverse events, and 2 with disease progression or Richter’s transformation.

At 15 months of follow-up, progression-free survival was 100% in patients who received the combination as the frontline therapy, and 83% in the patients with relapsed/refractory disease.

Adverse events

In the debulking phase, 34 patients (72%) experienced adverse events of any grade, including 16 patients with grade 3 or 4 events

Adverse events associated with debulking included neutropenia and anemia, each seen in five patients, thrombocytopenia and infection each seen in three patients, and coronary artery disorders, rash, tumor lysis syndrome, vomiting, and pyrexia in one patient each.

Sixty of the 66 patients received the full six induction cycles. Three patients who had fewer than two cycles were excluded according to protocol. Of these three, two heavily pretreated patients died of sepsis and one of myocardial infarction in cycle 1.

All but 3 of the 63 patients had an adverse event, and 44 patients had at least one grade 3 or 4 adverse event.

Cytopenias, infections, infusion-related reactions, and neoplasms were the most common adverse events.

There were three grade 3 laboratory-confirmed cases of tumor lysis syndrome, one each occurring during bendamustine debulking, obinutuzumab administration, and venetoclax administration.

Something other than venetoclax?

Davide Rossi, MD, PhD, of the Oncology Institute of Southern Switzerland in Bellinzona, the invited discussant, questioned whether venetoclax is the best agent to use in sequential triple-T therapy.

“We know that venetoclax is more active in blood and bone marrow than in lymph nodes and, indeed, a proportion of cases achieving all the criteria for a CR [complete response] in the bone marrow and the peripheral blood, including MRD negativity, may still have some residual [disease in] lymph nodes,” he said.

Drugs that inhibit the B-cell receptor pathway may be more effective at eradicating MRD in the lymph node compartment, Dr. Cramer said.

The study was sponsored by the German CLL study group. Dr. Cramer disclosed financial ties to multiple entities. Dr. Rossi did not report disclosures.
 

Natriuretic peptides have been shown to be valuable biomarkers for guiding diagnosis and treatment for cardiovascular disease. Recently, they also have been reported to inhibit progression of several cancers. The link is likely to be inflammation—which is usually a precursor to malignant changes, say researchers from Tokushima University and the National Cerebral and Cardiovascular Center Research Institute, both in Japan. To find out how reliable brain natriuretic peptide and C-reactive protein (CRP) levels might be in cancer, the researchers retrospectively studied 2,923 patients at their hospital who had had brain natriuretic peptide (BNP) measured to rule out heart disease.

Related: The Link Between Low-Density Lipoproteins and Chronic Lymphocytic Leukemia

Of 234 patients included in the final analysis, 80 were diagnosed with cancer. No patients with clinically evident heart failure and cardiac disease requiring medical treatment were included in the study. Both the plasma BNP and serum CRP levels were significantly higher in the patients with cancer (66.4 vs 44.0 pg/mL, and 0.99 vs 0.18 mg/dL, respectively). There were no significant differences in the echocardiographic parameters.

In 28 cured patients with solid cancers who underwent a radical surgery, the plasma BNP levels dropped significantly, from 70.7 to 45.0 pg/mL. However, the levels did not change after surgery in 7 relapsed or “insufficiently treated” patients with solid cancers. And although plasma BNP levels “tended to decrease” after chemotherapy in patients with hematologic cancers, in 13 patients plasma BNP levels did not change significantly.

Related: Novel Neuroendocrine Tumor in Multiple Endocrine Neoplasia Type 1

BNP levels were significantly higher in the patients with stage IV cancer, compared with those who had stages I, II, or III. This might be accompanied by systemic inflammation, the researchers say.

As far as the researchers know, no studies have shown that cancer cells generate BNP. Therefore, they think a higher plasma BNP level may reflect the elevated production from cardiomyocytes in association with inflammation in cancer patients.

Related: Pneumatic Tube-Induced Reverse Pseudohyperkalemia in a Patient With Chronic Lymphocytic Leukemia

Their findings suggest that it’s a good idea to consider the effect of cancer on the BNP levels when using BNP as an indicator of heart failure. Asymptomatic cancer patients with higher BNP levels should be diagnosed whether the elevated BNP is due to asymptomatic heart failure or cancer.

Source:

Bando S, Soeki T, Matsuura T, et al. PLoS One. 2017;12(6):e0178607

Natriuretic peptides have been shown to be valuable biomarkers for guiding diagnosis and treatment for cardiovascular disease. Recently, they also have been reported to inhibit progression of several cancers. The link is likely to be inflammation—which is usually a precursor to malignant changes, say researchers from Tokushima University and the National Cerebral and Cardiovascular Center Research Institute, both in Japan. To find out how reliable brain natriuretic peptide and C-reactive protein (CRP) levels might be in cancer, the researchers retrospectively studied 2,923 patients at their hospital who had had brain natriuretic peptide (BNP) measured to rule out heart disease.

Related: The Link Between Low-Density Lipoproteins and Chronic Lymphocytic Leukemia

Of 234 patients included in the final analysis, 80 were diagnosed with cancer. No patients with clinically evident heart failure and cardiac disease requiring medical treatment were included in the study. Both the plasma BNP and serum CRP levels were significantly higher in the patients with cancer (66.4 vs 44.0 pg/mL, and 0.99 vs 0.18 mg/dL, respectively). There were no significant differences in the echocardiographic parameters.

In 28 cured patients with solid cancers who underwent a radical surgery, the plasma BNP levels dropped significantly, from 70.7 to 45.0 pg/mL. However, the levels did not change after surgery in 7 relapsed or “insufficiently treated” patients with solid cancers. And although plasma BNP levels “tended to decrease” after chemotherapy in patients with hematologic cancers, in 13 patients plasma BNP levels did not change significantly.

Related: Novel Neuroendocrine Tumor in Multiple Endocrine Neoplasia Type 1

BNP levels were significantly higher in the patients with stage IV cancer, compared with those who had stages I, II, or III. This might be accompanied by systemic inflammation, the researchers say.

As far as the researchers know, no studies have shown that cancer cells generate BNP. Therefore, they think a higher plasma BNP level may reflect the elevated production from cardiomyocytes in association with inflammation in cancer patients.

Related: Pneumatic Tube-Induced Reverse Pseudohyperkalemia in a Patient With Chronic Lymphocytic Leukemia

Their findings suggest that it’s a good idea to consider the effect of cancer on the BNP levels when using BNP as an indicator of heart failure. Asymptomatic cancer patients with higher BNP levels should be diagnosed whether the elevated BNP is due to asymptomatic heart failure or cancer.

Source:

Bando S, Soeki T, Matsuura T, et al. PLoS One. 2017;12(6):e0178607

Natriuretic peptides have been shown to be valuable biomarkers for guiding diagnosis and treatment for cardiovascular disease. Recently, they also have been reported to inhibit progression of several cancers. The link is likely to be inflammation—which is usually a precursor to malignant changes, say researchers from Tokushima University and the National Cerebral and Cardiovascular Center Research Institute, both in Japan. To find out how reliable brain natriuretic peptide and C-reactive protein (CRP) levels might be in cancer, the researchers retrospectively studied 2,923 patients at their hospital who had had brain natriuretic peptide (BNP) measured to rule out heart disease.

Related: The Link Between Low-Density Lipoproteins and Chronic Lymphocytic Leukemia

Of 234 patients included in the final analysis, 80 were diagnosed with cancer. No patients with clinically evident heart failure and cardiac disease requiring medical treatment were included in the study. Both the plasma BNP and serum CRP levels were significantly higher in the patients with cancer (66.4 vs 44.0 pg/mL, and 0.99 vs 0.18 mg/dL, respectively). There were no significant differences in the echocardiographic parameters.

In 28 cured patients with solid cancers who underwent a radical surgery, the plasma BNP levels dropped significantly, from 70.7 to 45.0 pg/mL. However, the levels did not change after surgery in 7 relapsed or “insufficiently treated” patients with solid cancers. And although plasma BNP levels “tended to decrease” after chemotherapy in patients with hematologic cancers, in 13 patients plasma BNP levels did not change significantly.

Related: Novel Neuroendocrine Tumor in Multiple Endocrine Neoplasia Type 1

BNP levels were significantly higher in the patients with stage IV cancer, compared with those who had stages I, II, or III. This might be accompanied by systemic inflammation, the researchers say.

As far as the researchers know, no studies have shown that cancer cells generate BNP. Therefore, they think a higher plasma BNP level may reflect the elevated production from cardiomyocytes in association with inflammation in cancer patients.

Related: Pneumatic Tube-Induced Reverse Pseudohyperkalemia in a Patient With Chronic Lymphocytic Leukemia

Their findings suggest that it’s a good idea to consider the effect of cancer on the BNP levels when using BNP as an indicator of heart failure. Asymptomatic cancer patients with higher BNP levels should be diagnosed whether the elevated BNP is due to asymptomatic heart failure or cancer.

Source:

Bando S, Soeki T, Matsuura T, et al. PLoS One. 2017;12(6):e0178607

CHICAGO – CARs just keep getting better: In an early clinical trial, a chimeric antigen receptor (CAR) T-cell construct targeting B-cell maturation protein induced clinical remissions in 33 of 35 patients with relapsed/refractory multiple myeloma who were treated in an early clinical trial.

“In our current trials we have observed revolutionary, quick, and durable remissions in patients with multiple myeloma,” said Wanhong Zhao, MD, of the Second Affiliated Hospital of Xi’an (China) Jiaotong University.

CHICAGO – CARs just keep getting better: In an early clinical trial, a chimeric antigen receptor (CAR) T-cell construct targeting B-cell maturation protein induced clinical remissions in 33 of 35 patients with relapsed/refractory multiple myeloma who were treated in an early clinical trial.

“In our current trials we have observed revolutionary, quick, and durable remissions in patients with multiple myeloma,” said Wanhong Zhao, MD, of the Second Affiliated Hospital of Xi’an (China) Jiaotong University.

CHICAGO – CARs just keep getting better: In an early clinical trial, a chimeric antigen receptor (CAR) T-cell construct targeting B-cell maturation protein induced clinical remissions in 33 of 35 patients with relapsed/refractory multiple myeloma who were treated in an early clinical trial.

“In our current trials we have observed revolutionary, quick, and durable remissions in patients with multiple myeloma,” said Wanhong Zhao, MD, of the Second Affiliated Hospital of Xi’an (China) Jiaotong University.

Follicular lymphoma (FL), which accounts for about 20% to 30% of all non-Hodgkin lymphomas, is an incurable disease. Although people with FL are living longer, the median overall survival (OS) had been about 10 years—until recently. According to researchers from the Spanish Lymphoma Oncology Group, OS may be changing. In their long-term study of 1,074 patients with newly diagnosed FL, median OS was more than 20 years.

Related: Six Open Clinical Trials That Are Expanding Our Understanding of Immunotherapies

The difference, the researchers say, may be chemoimmunotherapy, specifically, the anti-CD20 monoclonal antibody rituximab. Patients were enrolled between 1980 and 2013 and followed for a median of 55 months. The researchers note that rituximab was added to the treatment options in 2003. When the researchers analyzed the patients who were still alive 10 years beyond the diagnosis, they found that 118 of 166 were free of evident clinical disease.

The prognostic factors the researchers enumerate are similar to those of other studies. The variables significantly associated with survival at 10 years were stage great than II, aged < 60 years, low Follicular Lymphoma International Prognostic Index, normal β2 microglobulin, no B symptoms on diagnosis, Performance Status 0 to 1, and treatment with anthracyclines and rituximab. But their data, the researchers add, support the conclusion that the initial combined treatment with rituximab and anthracyclines “could be considered key factors.” They note that randomized studies and meta-analyses have repeatedly made improvements in the survival of patients with FL.

Related: New Treatments Offer Hope in Diffuse Large B-Cell Lymphoma

“We believe that the weight of the introduction of [rituximab] in a young population, associated with chemotherapy,” the researchers say, “has given these high rates of survival in an unselected population.” They conclude, “in the [rituximab] era, the strategy of ‘wait and watch’ remains valid for patients with favorable prognostic factors and low-grade tumors.”

Source:
Provencio M, Sabín P, Gomez-Codina J, et al. PLoS One. 2017;12(5):e0177204.
doi: 10.1371/journal.pone.0177204

Follicular lymphoma (FL), which accounts for about 20% to 30% of all non-Hodgkin lymphomas, is an incurable disease. Although people with FL are living longer, the median overall survival (OS) had been about 10 years—until recently. According to researchers from the Spanish Lymphoma Oncology Group, OS may be changing. In their long-term study of 1,074 patients with newly diagnosed FL, median OS was more than 20 years.

Related: Six Open Clinical Trials That Are Expanding Our Understanding of Immunotherapies

The difference, the researchers say, may be chemoimmunotherapy, specifically, the anti-CD20 monoclonal antibody rituximab. Patients were enrolled between 1980 and 2013 and followed for a median of 55 months. The researchers note that rituximab was added to the treatment options in 2003. When the researchers analyzed the patients who were still alive 10 years beyond the diagnosis, they found that 118 of 166 were free of evident clinical disease.

The prognostic factors the researchers enumerate are similar to those of other studies. The variables significantly associated with survival at 10 years were stage great than II, aged < 60 years, low Follicular Lymphoma International Prognostic Index, normal β2 microglobulin, no B symptoms on diagnosis, Performance Status 0 to 1, and treatment with anthracyclines and rituximab. But their data, the researchers add, support the conclusion that the initial combined treatment with rituximab and anthracyclines “could be considered key factors.” They note that randomized studies and meta-analyses have repeatedly made improvements in the survival of patients with FL.

Related: New Treatments Offer Hope in Diffuse Large B-Cell Lymphoma

“We believe that the weight of the introduction of [rituximab] in a young population, associated with chemotherapy,” the researchers say, “has given these high rates of survival in an unselected population.” They conclude, “in the [rituximab] era, the strategy of ‘wait and watch’ remains valid for patients with favorable prognostic factors and low-grade tumors.”

Source:
Provencio M, Sabín P, Gomez-Codina J, et al. PLoS One. 2017;12(5):e0177204.
doi: 10.1371/journal.pone.0177204

Follicular lymphoma (FL), which accounts for about 20% to 30% of all non-Hodgkin lymphomas, is an incurable disease. Although people with FL are living longer, the median overall survival (OS) had been about 10 years—until recently. According to researchers from the Spanish Lymphoma Oncology Group, OS may be changing. In their long-term study of 1,074 patients with newly diagnosed FL, median OS was more than 20 years.

Related: Six Open Clinical Trials That Are Expanding Our Understanding of Immunotherapies

The difference, the researchers say, may be chemoimmunotherapy, specifically, the anti-CD20 monoclonal antibody rituximab. Patients were enrolled between 1980 and 2013 and followed for a median of 55 months. The researchers note that rituximab was added to the treatment options in 2003. When the researchers analyzed the patients who were still alive 10 years beyond the diagnosis, they found that 118 of 166 were free of evident clinical disease.

The prognostic factors the researchers enumerate are similar to those of other studies. The variables significantly associated with survival at 10 years were stage great than II, aged < 60 years, low Follicular Lymphoma International Prognostic Index, normal β2 microglobulin, no B symptoms on diagnosis, Performance Status 0 to 1, and treatment with anthracyclines and rituximab. But their data, the researchers add, support the conclusion that the initial combined treatment with rituximab and anthracyclines “could be considered key factors.” They note that randomized studies and meta-analyses have repeatedly made improvements in the survival of patients with FL.

Related: New Treatments Offer Hope in Diffuse Large B-Cell Lymphoma

“We believe that the weight of the introduction of [rituximab] in a young population, associated with chemotherapy,” the researchers say, “has given these high rates of survival in an unselected population.” They conclude, “in the [rituximab] era, the strategy of ‘wait and watch’ remains valid for patients with favorable prognostic factors and low-grade tumors.”

Source:
Provencio M, Sabín P, Gomez-Codina J, et al. PLoS One. 2017;12(5):e0177204.
doi: 10.1371/journal.pone.0177204

MONTREAL – Osteomyelitis is an especially challenging diagnosis in children with sickle cell disease (SCD) because the bone and joint signs, elevated white cell counts, and C-reactive protein levels that are commonly used to diagnose bone infection are frequently features of SCD as well.

As a result, most patients with SCD and suspected osteomyelitis are treated without a confirmation of the diagnosis.

A decade of data

The researchers set out to get a better handle on the characteristics and outcomes of osteomyelitis in patients with SCD and to see which laboratory and imaging findings might prove most useful for diagnosing osteomyelitis in this population. They reviewed data on 59 patients who were identified with indeterminate or likely osteomyelitis over a 10-year span. Of those, 30 were diagnosed and treated for osteomyelitis, and 29 were tentatively diagnosed but not treated. The latter group likely had symptoms caused by a bone infarction or vaso-occlusive crisis, Dr. Weisman said.

Among the 30 treated patients, osteomyelitis was confirmed by bone biopsy in 3, and an organism was isolated from blood or an abscess in 6. In the other 21, osteomyelitis was presumed based on clinical, laboratory, and MRI findings.

The median patient age was 12 years (range, 8 months to 18 years), 18 were male, and all but three patients have the HbSS genotype. Of the remaining patients, two had the HbSC and one the HbSF genotypes.

Infections occurred in the lower extremities in 11 patients, in the upper extremities in 10, in the pelvis or vertebrae in 2 each, and in the scapula, clavicle, hand, rib, or mandible in 1 patient each.

Just 13 of the 30 patients (43%) had lab findings of leukocytosis (more than 15,000 cells/mm²), and an equal number had elevated CRP (greater than 10 mg/L).

In contrast, 29 patients had an ESR above 20 mm/hour, and, in three of these patients, the rate was higher than 100 mm/hour.

When the researchers compared white blood cell counts and CRP levels between the treated patients and the 29 untreated controls, they found no significant differences for either measure of inflammation. In contrast, ESR was significantly higher among treated patients (P = .03).

Looking at the receiver operating characteristic curve for ESR, they found that an ESR of more than 100 mm/hour had 100% specificity for osteomyelitis in this group of patients.

Only 6 of the 30 (20%) had bacteremia. In 9 patients, nontyphoidal salmonella was isolated from cultures of either bone biopsy (3), abscess (3), or blood (6), but no possible causative organism could be isolated in the remaining 21 patients.

All patients were treated with prolonged antibiotic therapy. Surgical drainage and/or debridement were required in 6 patients. Two patients developed chronic osteomyelitis, but infection eventually resolved in all patients.

Recommendations

Dr. Weisman recommended early consultation with infectious disease experts and orthopedists; labs studies with complete blood counts, CRP, and ESR; and imaging studies with MRI when there is clinical suspicion of osteomyelitis in patients with SCD.

When an SCD patient has indeterminate findings, a blood culture can be performed. If it is positive for salmonella and the ESR is above 100 mm/hour, the patient can then go on to treatment. If the blood culture is negative and the ESR is below 100 mm hour but the suspicion of osteomyelitis remains high, a bone biopsy can be considered, they concluded.

The study was internally funded. Dr. Weisman reported no conflicts of interest to disclose.

MONTREAL – Osteomyelitis is an especially challenging diagnosis in children with sickle cell disease (SCD) because the bone and joint signs, elevated white cell counts, and C-reactive protein levels that are commonly used to diagnose bone infection are frequently features of SCD as well.

As a result, most patients with SCD and suspected osteomyelitis are treated without a confirmation of the diagnosis.

A decade of data

The researchers set out to get a better handle on the characteristics and outcomes of osteomyelitis in patients with SCD and to see which laboratory and imaging findings might prove most useful for diagnosing osteomyelitis in this population. They reviewed data on 59 patients who were identified with indeterminate or likely osteomyelitis over a 10-year span. Of those, 30 were diagnosed and treated for osteomyelitis, and 29 were tentatively diagnosed but not treated. The latter group likely had symptoms caused by a bone infarction or vaso-occlusive crisis, Dr. Weisman said.

Among the 30 treated patients, osteomyelitis was confirmed by bone biopsy in 3, and an organism was isolated from blood or an abscess in 6. In the other 21, osteomyelitis was presumed based on clinical, laboratory, and MRI findings.

The median patient age was 12 years (range, 8 months to 18 years), 18 were male, and all but three patients have the HbSS genotype. Of the remaining patients, two had the HbSC and one the HbSF genotypes.

Infections occurred in the lower extremities in 11 patients, in the upper extremities in 10, in the pelvis or vertebrae in 2 each, and in the scapula, clavicle, hand, rib, or mandible in 1 patient each.

Just 13 of the 30 patients (43%) had lab findings of leukocytosis (more than 15,000 cells/mm²), and an equal number had elevated CRP (greater than 10 mg/L).

In contrast, 29 patients had an ESR above 20 mm/hour, and, in three of these patients, the rate was higher than 100 mm/hour.

When the researchers compared white blood cell counts and CRP levels between the treated patients and the 29 untreated controls, they found no significant differences for either measure of inflammation. In contrast, ESR was significantly higher among treated patients (P = .03).

Looking at the receiver operating characteristic curve for ESR, they found that an ESR of more than 100 mm/hour had 100% specificity for osteomyelitis in this group of patients.

Only 6 of the 30 (20%) had bacteremia. In 9 patients, nontyphoidal salmonella was isolated from cultures of either bone biopsy (3), abscess (3), or blood (6), but no possible causative organism could be isolated in the remaining 21 patients.

All patients were treated with prolonged antibiotic therapy. Surgical drainage and/or debridement were required in 6 patients. Two patients developed chronic osteomyelitis, but infection eventually resolved in all patients.

Recommendations

Dr. Weisman recommended early consultation with infectious disease experts and orthopedists; labs studies with complete blood counts, CRP, and ESR; and imaging studies with MRI when there is clinical suspicion of osteomyelitis in patients with SCD.

When an SCD patient has indeterminate findings, a blood culture can be performed. If it is positive for salmonella and the ESR is above 100 mm/hour, the patient can then go on to treatment. If the blood culture is negative and the ESR is below 100 mm hour but the suspicion of osteomyelitis remains high, a bone biopsy can be considered, they concluded.

The study was internally funded. Dr. Weisman reported no conflicts of interest to disclose.

MONTREAL – Osteomyelitis is an especially challenging diagnosis in children with sickle cell disease (SCD) because the bone and joint signs, elevated white cell counts, and C-reactive protein levels that are commonly used to diagnose bone infection are frequently features of SCD as well.

As a result, most patients with SCD and suspected osteomyelitis are treated without a confirmation of the diagnosis.

A decade of data

The researchers set out to get a better handle on the characteristics and outcomes of osteomyelitis in patients with SCD and to see which laboratory and imaging findings might prove most useful for diagnosing osteomyelitis in this population. They reviewed data on 59 patients who were identified with indeterminate or likely osteomyelitis over a 10-year span. Of those, 30 were diagnosed and treated for osteomyelitis, and 29 were tentatively diagnosed but not treated. The latter group likely had symptoms caused by a bone infarction or vaso-occlusive crisis, Dr. Weisman said.

Among the 30 treated patients, osteomyelitis was confirmed by bone biopsy in 3, and an organism was isolated from blood or an abscess in 6. In the other 21, osteomyelitis was presumed based on clinical, laboratory, and MRI findings.

The median patient age was 12 years (range, 8 months to 18 years), 18 were male, and all but three patients have the HbSS genotype. Of the remaining patients, two had the HbSC and one the HbSF genotypes.

Infections occurred in the lower extremities in 11 patients, in the upper extremities in 10, in the pelvis or vertebrae in 2 each, and in the scapula, clavicle, hand, rib, or mandible in 1 patient each.

Just 13 of the 30 patients (43%) had lab findings of leukocytosis (more than 15,000 cells/mm²), and an equal number had elevated CRP (greater than 10 mg/L).

In contrast, 29 patients had an ESR above 20 mm/hour, and, in three of these patients, the rate was higher than 100 mm/hour.

When the researchers compared white blood cell counts and CRP levels between the treated patients and the 29 untreated controls, they found no significant differences for either measure of inflammation. In contrast, ESR was significantly higher among treated patients (P = .03).

Looking at the receiver operating characteristic curve for ESR, they found that an ESR of more than 100 mm/hour had 100% specificity for osteomyelitis in this group of patients.

Only 6 of the 30 (20%) had bacteremia. In 9 patients, nontyphoidal salmonella was isolated from cultures of either bone biopsy (3), abscess (3), or blood (6), but no possible causative organism could be isolated in the remaining 21 patients.

All patients were treated with prolonged antibiotic therapy. Surgical drainage and/or debridement were required in 6 patients. Two patients developed chronic osteomyelitis, but infection eventually resolved in all patients.

Recommendations

Dr. Weisman recommended early consultation with infectious disease experts and orthopedists; labs studies with complete blood counts, CRP, and ESR; and imaging studies with MRI when there is clinical suspicion of osteomyelitis in patients with SCD.

When an SCD patient has indeterminate findings, a blood culture can be performed. If it is positive for salmonella and the ESR is above 100 mm/hour, the patient can then go on to treatment. If the blood culture is negative and the ESR is below 100 mm hour but the suspicion of osteomyelitis remains high, a bone biopsy can be considered, they concluded.

The study was internally funded. Dr. Weisman reported no conflicts of interest to disclose.

A diagnosis of chronic lymphocytic leukemia (CLL) usually occurs in people aged ≥ 72 years. But most clinical trials do not reflect that reality; thus, treatments and prognoses are based on younger patients’ experiences. Researchers from University of Pennsylvania, Emory University in Georgia, NorthShore University HealthSystem in Illinois, New York-Presbyterian Hospital/Columbia University Medical Center, Thomas Jefferson University in Pennsylvania, and Dana-Farber Cancer Institute in Massachusetts, conducted the largest comprehensive prospective evaluation of this patient population published to date to their knowledge to examine treatment patterns, outcomes, and disease-related mortality in CLL patients aged  ≥ 75 years in a real-world setting.

The researchers analyzed data from patients in the Connect® CLL registry, a prospective observational cohort study that took place between 2010 and 2014 at 199 U.S. sites. Of 1,494 patients enrolled in the registry, 259 patients aged  ≥ 75 years were enrolled within 2 months of starting first- line of therapy (LOT1), and 196 were enrolled in a subsequent line of therapy (LOT ≥ 2). The patients were almost entirely enrolled prior to the introduction of novel B-cell receptor-targeted therapies. The researchers say they aimed to establish a benchmark for outcomes in elderly patients with CLL who were treated before those therapies to help properly position newer agents in the treatment paradigm.

They found that elderly patients with CLL were more likely than were younger patients to receive rituximab monotherapy. In LOT ≥ 2 they were significantly less likely to receive bendamustine/rituximab. Only 6.9% of patients aged > 75 years received fludarabine/cyclophosphamide/rituximab, vs 33.7% of patients aged < 75 years. Interestingly, the researchers add, older patients were significantly more likely than were younger patients to receive chemotherapy alone without anti-CD20 antibody therapy.

Serious adverse events were more common in the elderly patients. Pneumonia was more common in elderly patients in LOT1; in LOT ≥ 2, rates of pneumonia were similar in both groups. In the follow-up with a median of 32.6 months, 433 of the 1,494 patients had died. Only 5% of patients aged < 75 years in LOT1 died of CLL, compared with 13% of elderly patients. Time to death from CLL or infection was also significantly shorter in patients aged > 75 years, compared with patients aged < 75 years. When stratified by risk, mortality due to CLL or infection was 10.3% in the lower risk group compared with 30.6% in the higher risk group.

The researchers identified 3 prognostic indicators: < 3 months from diagnosis to first treatment, enrollment therapy other than bendamustine/rituximab, and anemia. The researchers say the higher risk of CLL- or infection-related death has not, to their knowledge, been reported previously. This finding, they say, “highlights the urgent need for therapies tailored to this population.” Current therapies and strategies, they note, “appear suboptimal.”

Source:
Nabhan C, Mato A, Flowers CR, et al. BMC Cancer. 2017;17(1):198.
doi: 10.1186/s12885-017-3176-x.

A diagnosis of chronic lymphocytic leukemia (CLL) usually occurs in people aged ≥ 72 years. But most clinical trials do not reflect that reality; thus, treatments and prognoses are based on younger patients’ experiences. Researchers from University of Pennsylvania, Emory University in Georgia, NorthShore University HealthSystem in Illinois, New York-Presbyterian Hospital/Columbia University Medical Center, Thomas Jefferson University in Pennsylvania, and Dana-Farber Cancer Institute in Massachusetts, conducted the largest comprehensive prospective evaluation of this patient population published to date to their knowledge to examine treatment patterns, outcomes, and disease-related mortality in CLL patients aged  ≥ 75 years in a real-world setting.

The researchers analyzed data from patients in the Connect® CLL registry, a prospective observational cohort study that took place between 2010 and 2014 at 199 U.S. sites. Of 1,494 patients enrolled in the registry, 259 patients aged  ≥ 75 years were enrolled within 2 months of starting first- line of therapy (LOT1), and 196 were enrolled in a subsequent line of therapy (LOT ≥ 2). The patients were almost entirely enrolled prior to the introduction of novel B-cell receptor-targeted therapies. The researchers say they aimed to establish a benchmark for outcomes in elderly patients with CLL who were treated before those therapies to help properly position newer agents in the treatment paradigm.

They found that elderly patients with CLL were more likely than were younger patients to receive rituximab monotherapy. In LOT ≥ 2 they were significantly less likely to receive bendamustine/rituximab. Only 6.9% of patients aged > 75 years received fludarabine/cyclophosphamide/rituximab, vs 33.7% of patients aged < 75 years. Interestingly, the researchers add, older patients were significantly more likely than were younger patients to receive chemotherapy alone without anti-CD20 antibody therapy.

Serious adverse events were more common in the elderly patients. Pneumonia was more common in elderly patients in LOT1; in LOT ≥ 2, rates of pneumonia were similar in both groups. In the follow-up with a median of 32.6 months, 433 of the 1,494 patients had died. Only 5% of patients aged < 75 years in LOT1 died of CLL, compared with 13% of elderly patients. Time to death from CLL or infection was also significantly shorter in patients aged > 75 years, compared with patients aged < 75 years. When stratified by risk, mortality due to CLL or infection was 10.3% in the lower risk group compared with 30.6% in the higher risk group.

The researchers identified 3 prognostic indicators: < 3 months from diagnosis to first treatment, enrollment therapy other than bendamustine/rituximab, and anemia. The researchers say the higher risk of CLL- or infection-related death has not, to their knowledge, been reported previously. This finding, they say, “highlights the urgent need for therapies tailored to this population.” Current therapies and strategies, they note, “appear suboptimal.”

Source:
Nabhan C, Mato A, Flowers CR, et al. BMC Cancer. 2017;17(1):198.
doi: 10.1186/s12885-017-3176-x.

A diagnosis of chronic lymphocytic leukemia (CLL) usually occurs in people aged ≥ 72 years. But most clinical trials do not reflect that reality; thus, treatments and prognoses are based on younger patients’ experiences. Researchers from University of Pennsylvania, Emory University in Georgia, NorthShore University HealthSystem in Illinois, New York-Presbyterian Hospital/Columbia University Medical Center, Thomas Jefferson University in Pennsylvania, and Dana-Farber Cancer Institute in Massachusetts, conducted the largest comprehensive prospective evaluation of this patient population published to date to their knowledge to examine treatment patterns, outcomes, and disease-related mortality in CLL patients aged  ≥ 75 years in a real-world setting.

The researchers analyzed data from patients in the Connect® CLL registry, a prospective observational cohort study that took place between 2010 and 2014 at 199 U.S. sites. Of 1,494 patients enrolled in the registry, 259 patients aged  ≥ 75 years were enrolled within 2 months of starting first- line of therapy (LOT1), and 196 were enrolled in a subsequent line of therapy (LOT ≥ 2). The patients were almost entirely enrolled prior to the introduction of novel B-cell receptor-targeted therapies. The researchers say they aimed to establish a benchmark for outcomes in elderly patients with CLL who were treated before those therapies to help properly position newer agents in the treatment paradigm.

They found that elderly patients with CLL were more likely than were younger patients to receive rituximab monotherapy. In LOT ≥ 2 they were significantly less likely to receive bendamustine/rituximab. Only 6.9% of patients aged > 75 years received fludarabine/cyclophosphamide/rituximab, vs 33.7% of patients aged < 75 years. Interestingly, the researchers add, older patients were significantly more likely than were younger patients to receive chemotherapy alone without anti-CD20 antibody therapy.

Serious adverse events were more common in the elderly patients. Pneumonia was more common in elderly patients in LOT1; in LOT ≥ 2, rates of pneumonia were similar in both groups. In the follow-up with a median of 32.6 months, 433 of the 1,494 patients had died. Only 5% of patients aged < 75 years in LOT1 died of CLL, compared with 13% of elderly patients. Time to death from CLL or infection was also significantly shorter in patients aged > 75 years, compared with patients aged < 75 years. When stratified by risk, mortality due to CLL or infection was 10.3% in the lower risk group compared with 30.6% in the higher risk group.

The researchers identified 3 prognostic indicators: < 3 months from diagnosis to first treatment, enrollment therapy other than bendamustine/rituximab, and anemia. The researchers say the higher risk of CLL- or infection-related death has not, to their knowledge, been reported previously. This finding, they say, “highlights the urgent need for therapies tailored to this population.” Current therapies and strategies, they note, “appear suboptimal.”

Source:
Nabhan C, Mato A, Flowers CR, et al. BMC Cancer. 2017;17(1):198.
doi: 10.1186/s12885-017-3176-x.