RIT can improve transplant outcomes in NHL, CLL

GRAPEVINE, TEXAS—Administering radioimmunotherapy (RIT) prior to non-myeloablative allogeneic transplant (NMAT) can improve survival in patients with persistent disease, according to a speaker at the 2014 BMT Tandem Meetings.

Ryan Cassaday, MD, of the University of Washington in Seattle, noted that RIT-augmented NMAT can produce long-term remissions in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) or chronic lymphocytic leukemia (CLL).

But outcomes for patients with persistent disease are “underdescribed.”

So he and his colleagues set out to describe outcomes of NMAT for patients with persistent indolent B-NHL or CLL and estimate the impact of RIT in these patients.

Treatment details

The researchers retrospectively analyzed data from 89 patients who underwent NMAT from December 1998 to April 2009 and were followed until September 2013. Eighteen of the patients had received RIT as part of a prospective study (AK Gopal et al, Blood 2011).

The remaining 71 patients did not receive RIT but met eligibility criteria for that study. Specifically, they had a CD20+ B-cell malignancy, an HLA-matched peripheral blood stem cell donor, and persistent disease at NMAT. These control subjects received fludarabine (30 mg/m² on days -7, -6, and -5) and 2 Gy of total body irradiation prior to NMAT.

Patients in the RIT group received the same treatment following RIT. On day -21, they received 250 mg/m² of rituximab before an imaging dose of ¹¹¹In-ibritumomab tiuxetan. And on day -14, they received 250 mg/m² of rituximab and 0.4 mCi/kg of ⁹⁰Y-ibritumomab tiuxetan.

Patient characteristics

In the RIT group, 10 patients had CLL/small lymphocytic lymphoma (SLL), 6 had follicular lymphoma (FL), 1 had marginal zone lymphoma (MZL), and 1 had hairy cell leukemia. As for controls, 52 had CLL/SLL, 18 had FL, and 1 had MZL.

“The majority of patients were male [74%] and a relatively young age, given the diseases being treated [median of 56 years],” Dr Cassaday said. “The majority of patients had previously received rituximab [88%], and patients were heavily pretreated [median of 4 prior therapies, range 1-12].”

There were no significant differences between the 2 treatment groups with regard to the aforementioned characteristics. However, there were some “striking differences” between the 2 groups, Dr Cassaday said, including characteristics that portend worse prognosis.

Specifically, RIT-treated patients had more bulky disease (> 5 cm) than controls (61% vs 15%, P<0.001) and more chemoresistant disease (81% vs 39%, P=0.003). And RIT patients were more likely to have HCT comorbidity index scores of 3 or higher (72% vs 37%, P=0.006), as well as pre-NMAT platelet counts less than 25k/μL (33% vs 7%, P=0.002).

RIT improves PFS, OS

The researchers conducted a multivariate analysis including the factors that differed significantly between the 2 treatment groups. And they found that only RIT was significantly associated with both progression-free survival (PFS) and overall survival (OS).

When calculating survival curves, the researchers adjusted for the imbalance in covariates between the treatment groups.

“[The adjusted survival rate] is essentially what one might expect had the RIT group had similar baseline characteristics as the control group,” Dr Cassaday explained.

Control subjects had a 3-year OS of 55%. For the RIT-treated patients, the unadjusted 3-year OS was 78% (P=0.20), and the adjusted OS was 87% (P=0.008).

The 3-year PFS was 44% for controls. For the RIT group, the unadjusted 3-year PFS was 56% (P=0.36), and the adjusted PFS was 71% (P=0.02).

The researchers also found that RIT did not increase the rate of non-relapse mortality. The unadjusted hazard ratio was 0.5 (P=0.32), and the adjusted hazard ratio was 0.4 (P=0.18).

“This analysis does have some limitations,” Dr Cassaday conceded. “Clearly, it does not replace the strength of evidence that would come from a randomized, controlled trial. And the relatively small sample size does limit our ability to look at a lot of different subgroups.”

In addition, the findings may not apply to other non-myeloablative regimens. And, due to the time frame of the study, the researchers could not account for the potential impact of newer agents.

Nevertheless, Dr Cassaday said the data suggest that RIT can improve the outcome of NMAT in patients with persistent indolent B-NHL or CLL. And a prospective, randomized study evaluating this approach is warranted.

Dr Cassaday presented this research at the 2014 BMT Tandem Meetings as abstract 75. Information in the abstract differs from that presented.

GRAPEVINE, TEXAS—Administering radioimmunotherapy (RIT) prior to non-myeloablative allogeneic transplant (NMAT) can improve survival in patients with persistent disease, according to a speaker at the 2014 BMT Tandem Meetings.

Ryan Cassaday, MD, of the University of Washington in Seattle, noted that RIT-augmented NMAT can produce long-term remissions in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) or chronic lymphocytic leukemia (CLL).

But outcomes for patients with persistent disease are “underdescribed.”

So he and his colleagues set out to describe outcomes of NMAT for patients with persistent indolent B-NHL or CLL and estimate the impact of RIT in these patients.

Treatment details

The researchers retrospectively analyzed data from 89 patients who underwent NMAT from December 1998 to April 2009 and were followed until September 2013. Eighteen of the patients had received RIT as part of a prospective study (AK Gopal et al, Blood 2011).

The remaining 71 patients did not receive RIT but met eligibility criteria for that study. Specifically, they had a CD20+ B-cell malignancy, an HLA-matched peripheral blood stem cell donor, and persistent disease at NMAT. These control subjects received fludarabine (30 mg/m² on days -7, -6, and -5) and 2 Gy of total body irradiation prior to NMAT.

Patients in the RIT group received the same treatment following RIT. On day -21, they received 250 mg/m² of rituximab before an imaging dose of ¹¹¹In-ibritumomab tiuxetan. And on day -14, they received 250 mg/m² of rituximab and 0.4 mCi/kg of ⁹⁰Y-ibritumomab tiuxetan.

Patient characteristics

In the RIT group, 10 patients had CLL/small lymphocytic lymphoma (SLL), 6 had follicular lymphoma (FL), 1 had marginal zone lymphoma (MZL), and 1 had hairy cell leukemia. As for controls, 52 had CLL/SLL, 18 had FL, and 1 had MZL.

“The majority of patients were male [74%] and a relatively young age, given the diseases being treated [median of 56 years],” Dr Cassaday said. “The majority of patients had previously received rituximab [88%], and patients were heavily pretreated [median of 4 prior therapies, range 1-12].”

There were no significant differences between the 2 treatment groups with regard to the aforementioned characteristics. However, there were some “striking differences” between the 2 groups, Dr Cassaday said, including characteristics that portend worse prognosis.

Specifically, RIT-treated patients had more bulky disease (> 5 cm) than controls (61% vs 15%, P<0.001) and more chemoresistant disease (81% vs 39%, P=0.003). And RIT patients were more likely to have HCT comorbidity index scores of 3 or higher (72% vs 37%, P=0.006), as well as pre-NMAT platelet counts less than 25k/μL (33% vs 7%, P=0.002).

RIT improves PFS, OS

The researchers conducted a multivariate analysis including the factors that differed significantly between the 2 treatment groups. And they found that only RIT was significantly associated with both progression-free survival (PFS) and overall survival (OS).

When calculating survival curves, the researchers adjusted for the imbalance in covariates between the treatment groups.

“[The adjusted survival rate] is essentially what one might expect had the RIT group had similar baseline characteristics as the control group,” Dr Cassaday explained.

Control subjects had a 3-year OS of 55%. For the RIT-treated patients, the unadjusted 3-year OS was 78% (P=0.20), and the adjusted OS was 87% (P=0.008).

The 3-year PFS was 44% for controls. For the RIT group, the unadjusted 3-year PFS was 56% (P=0.36), and the adjusted PFS was 71% (P=0.02).

The researchers also found that RIT did not increase the rate of non-relapse mortality. The unadjusted hazard ratio was 0.5 (P=0.32), and the adjusted hazard ratio was 0.4 (P=0.18).

“This analysis does have some limitations,” Dr Cassaday conceded. “Clearly, it does not replace the strength of evidence that would come from a randomized, controlled trial. And the relatively small sample size does limit our ability to look at a lot of different subgroups.”

In addition, the findings may not apply to other non-myeloablative regimens. And, due to the time frame of the study, the researchers could not account for the potential impact of newer agents.

Nevertheless, Dr Cassaday said the data suggest that RIT can improve the outcome of NMAT in patients with persistent indolent B-NHL or CLL. And a prospective, randomized study evaluating this approach is warranted.

Dr Cassaday presented this research at the 2014 BMT Tandem Meetings as abstract 75. Information in the abstract differs from that presented.

GRAPEVINE, TEXAS—Administering radioimmunotherapy (RIT) prior to non-myeloablative allogeneic transplant (NMAT) can improve survival in patients with persistent disease, according to a speaker at the 2014 BMT Tandem Meetings.

Ryan Cassaday, MD, of the University of Washington in Seattle, noted that RIT-augmented NMAT can produce long-term remissions in patients with relapsed or refractory B-cell non-Hodgkin lymphoma (B-NHL) or chronic lymphocytic leukemia (CLL).

But outcomes for patients with persistent disease are “underdescribed.”

So he and his colleagues set out to describe outcomes of NMAT for patients with persistent indolent B-NHL or CLL and estimate the impact of RIT in these patients.

Treatment details

The researchers retrospectively analyzed data from 89 patients who underwent NMAT from December 1998 to April 2009 and were followed until September 2013. Eighteen of the patients had received RIT as part of a prospective study (AK Gopal et al, Blood 2011).

The remaining 71 patients did not receive RIT but met eligibility criteria for that study. Specifically, they had a CD20+ B-cell malignancy, an HLA-matched peripheral blood stem cell donor, and persistent disease at NMAT. These control subjects received fludarabine (30 mg/m² on days -7, -6, and -5) and 2 Gy of total body irradiation prior to NMAT.

Patients in the RIT group received the same treatment following RIT. On day -21, they received 250 mg/m² of rituximab before an imaging dose of ¹¹¹In-ibritumomab tiuxetan. And on day -14, they received 250 mg/m² of rituximab and 0.4 mCi/kg of ⁹⁰Y-ibritumomab tiuxetan.

Patient characteristics

In the RIT group, 10 patients had CLL/small lymphocytic lymphoma (SLL), 6 had follicular lymphoma (FL), 1 had marginal zone lymphoma (MZL), and 1 had hairy cell leukemia. As for controls, 52 had CLL/SLL, 18 had FL, and 1 had MZL.

“The majority of patients were male [74%] and a relatively young age, given the diseases being treated [median of 56 years],” Dr Cassaday said. “The majority of patients had previously received rituximab [88%], and patients were heavily pretreated [median of 4 prior therapies, range 1-12].”

There were no significant differences between the 2 treatment groups with regard to the aforementioned characteristics. However, there were some “striking differences” between the 2 groups, Dr Cassaday said, including characteristics that portend worse prognosis.

Specifically, RIT-treated patients had more bulky disease (> 5 cm) than controls (61% vs 15%, P<0.001) and more chemoresistant disease (81% vs 39%, P=0.003). And RIT patients were more likely to have HCT comorbidity index scores of 3 or higher (72% vs 37%, P=0.006), as well as pre-NMAT platelet counts less than 25k/μL (33% vs 7%, P=0.002).

RIT improves PFS, OS

The researchers conducted a multivariate analysis including the factors that differed significantly between the 2 treatment groups. And they found that only RIT was significantly associated with both progression-free survival (PFS) and overall survival (OS).

When calculating survival curves, the researchers adjusted for the imbalance in covariates between the treatment groups.

“[The adjusted survival rate] is essentially what one might expect had the RIT group had similar baseline characteristics as the control group,” Dr Cassaday explained.

Control subjects had a 3-year OS of 55%. For the RIT-treated patients, the unadjusted 3-year OS was 78% (P=0.20), and the adjusted OS was 87% (P=0.008).

The 3-year PFS was 44% for controls. For the RIT group, the unadjusted 3-year PFS was 56% (P=0.36), and the adjusted PFS was 71% (P=0.02).

The researchers also found that RIT did not increase the rate of non-relapse mortality. The unadjusted hazard ratio was 0.5 (P=0.32), and the adjusted hazard ratio was 0.4 (P=0.18).

“This analysis does have some limitations,” Dr Cassaday conceded. “Clearly, it does not replace the strength of evidence that would come from a randomized, controlled trial. And the relatively small sample size does limit our ability to look at a lot of different subgroups.”

In addition, the findings may not apply to other non-myeloablative regimens. And, due to the time frame of the study, the researchers could not account for the potential impact of newer agents.

Nevertheless, Dr Cassaday said the data suggest that RIT can improve the outcome of NMAT in patients with persistent indolent B-NHL or CLL. And a prospective, randomized study evaluating this approach is warranted.

Dr Cassaday presented this research at the 2014 BMT Tandem Meetings as abstract 75. Information in the abstract differs from that presented.