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No Difference in CNS Relapse Rate According to Prophylaxis Route
According to results from a retrospective analysis of central nervous system ( CNS ) prophylaxis in patients with aggressive non-Hodgkin lymphomas ( NHLs ), rates of CNS relapse did not differ according to intrathecal ( IT ) or intravenous ( IV ) administration . The analysis , presented at the 2020 ASH Annual Meeting by Victor M . Orellana-Noia , MD , from Emory University in Atlanta , Georgia , also highlighted factors predictive of CNS relapse that are missing from conventional scoring systems .
These results accompanied other data presented at the meeting that demonstrated that high-dose methotrexate did not lower the risk of CNS relapse in high-risk diffuse large B-cell lymphoma , despite current recommendations for prophylactic IV high-dose methotrexate in this population .
To determine whether route of prophylaxis affected CNS relapse , Dr . Orellana-Noia and colleagues performed a multicenter retrospective analysis of patients with aggressive NHL ( excluding Burkitt lymphoma ) who received single-route CNS prophylaxis during frontline anthracycline-based therapy between 2013 and 2019 across 19 U . S . academic institutions .
The authors identified a total of 1,056 patients who received CNS prophylaxis . Twentyeight were excluded after they switched routes due to toxicity , leaving 1,024 patients in the analysis : 216 who received IV prophylaxis and 808 who received IT prophylaxis .
Patients ’ median ages were 57 years in the IV cohort and 59 years in the IT cohort . Incidence of renal impairment was slightly lower in the IV group ( 12 % vs . 16 %), while incidence of double-hit lymphoma was slightly higher in the IT group ( 8.3 % vs . 16 %).
The CNS International Prognostic Index ( IPI ) predicted a relapse rate of 6.13 % across the entire population , however , the observed CNS relapse rate was 5.5 %, regardless of type of prophylaxis ( 5.3 % in the IT group vs . 7.1 % in the IV group ; p = 0.18 ).
This lack of difference persisted across all subgroups , including age , stage , CNS-IPI score , and double-hit status , the researchers noted .
Looking at the predictive value of the six CNS-IPI components , only two [ elevated serum lactate dehydrogenase ( LDH ) and number of extranodal sites involved ] were significantly associated with CNS relapse . In addition , while CNS-IPI discriminated CNS relapse risk among those with high versus moderate risk , it was a poor predictor for some groups with low risk ( TABLE ). “ Our low-risk group had a significantly higher observed CNS relapse risk , which was fascinating to see ,” Dr . Orellana-Noia reported .
Based on these data , the researchers were able to identify four factors that were significantly associated with higher CNS relapse risk in univariate analysis : testicular involvement , elevated LDH , high extranodal disease burden , and liver involvement .
In a multivariate model , only testicular involvement and elevated serum LDH continued to predict for CNS relapse :
• testicular involvement : 5.38 ( p = 0.067 )
• LDH > upper limit of normal : 2.70 ( p = 0.018 )
• > 1 extranodal site : 1.39 ( p = 0.32 )
• liver involvement : 1.95 ( p = 0.067 )
However , Dr . Orellana-Noia noted that median CNS-IPI scores were higher among patients with liver involvement , suggesting that the CNS risk with liver involvement may already be captured by conventional scoring systems . “ In contrast , those with testicular involvement had , on average , lower CNS-IPI scores , [ which ] appears to show a shortcoming in the models we are using to risk-stratify patients ,” he said .
Among those who developed CNS relapse despite prophylaxis , there was no significant difference in time to relapse with either administration , but each group had a somewhat longer time to event than historical references , Dr . Orellana-Noia noted . “ There are still a number of early CNS relapse events despite prophylaxis … and overall survival remains very poor when relapse occurs ( at 7.1 months ) with no significant benefit from salvage therapy ,” he added .
“ CNS relapse is a rare , but devastating complication , [ which ] highlights the need to optimize and standardize our approach to CNS prophylaxis ,” Dr . Orellana-Noia concluded . In that vein , future studies are planned to evaluate single- versus dual-route of administration , as well as the value of prophylaxis versus no prophylaxis .
Study authors report no relevant conflicts of interest .
Reference Orellana-Noia VM , Reed DR , Sen JM , et al . CNS prophylaxis during frontline therapy in aggressive non-Hodgkin lymphomas : real-world outcomes and practice patterns from 19 US academic institutions . Abstract # 478 . Presented at the 2020 American Society of Hematology Annual Meeting , December 6 , 2020 .
TABLE . Relapses Predicted With CNS-IPI Versus Observed Relapses
CNS-IPI Score N Predicted Observed Low 190 3 % 5.3 % Moderate 527 5 % 3.9 % High 307 10 % 8.1 %
TPO-RAs and ITP : Eltrombopag Induces High Efficacy , But Avatrombopag Offers Advantages
A pair of studies presented at the 2020 ASH Annual Meeting analyzed the thrombopoietin receptor agonist ( TPO-RA ) eltrombopag in two settings : in real-world clinical practice against clinical trials experiences , and against another TPO-RA , avatrombopag .
Eltrombopag in Real-World Clinical Practice
Since 2010 , eltrombopag has been available in Europe for the management of chronic primary immune thrombocytopenia ( ITP ), but efficacy data regarding its use has largely been limited to the confines of clinical trials . 1 In a study presented by Guillaume Moulis , MD , PhD , of Toulouse University Hospital in France , real-world clinical practice data show eltrombopag is typically used early in the course of ITP in France , and overall efficacy of the therapy is comparable to that observed in clinical trials .
Dr . Moulis shared findings from the ELEXTRA study , which evaluated outcomes among 156 patients with ITP who had been exposed to eltrombopag and were enrolled in the CARMEN-France registry between 2013 and 2019 . Investigators followed all patients through routine clinic visits or hospitalizations .
The median platelet count at the time of ITP diagnosis was 8 × 10 9 / L , and approximately three-quarters of patients had bleeding .
The median time between ITP onset and first administration of eltrombopag was 3.3 months ( range = 0.1-82.2 months ). The median duration of eltrombopag exposure was 100 days ( range = 1-1,427 days ). At the time of starting eltrombopag , 75 patients ( 48.1 %) had a platelet count < 30 × 10 9 / L and were included in the efficacy analysis . Most of these patients ( n = 65 ; 86.7 %) responded to therapy , reaching platelet levels ≥30 × 10 9 / L , and 53 patients ( 70.7 %) experienced a complete response at any time during treatment exposure .
Most responders were taking concomitant therapies at the time of starting eltrombopag ( n = 58 ; 89.2 %), the authors reported .
Forty-seven adverse events ( AEs ) were reported in the registry ; the most frequently reported AEs included thrombocytosis ( n = 10 ), thrombosis ( n = 8 ), rash ( n = 4 ), hepatitis ( n = 3 ), and headache ( n = 3 ). The safety profile of eltrombopag observed in this real-world analysis was similar to that reported in the drug ’ s clinical trials , Dr . Moulis and coauthors observed .
Eltrombopag Versus Avatrombopag
In the second presentation , Michael D . Tarantino , MD , from the Bleeding & Clotting Disorders Institute in Peoria , Illinois , discussed eltrombopag in the context of avatrombopag , another approved TPO-RA that also has established efficacy in ITP ,
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38 ASH Clinical News March 2021