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[Haematologica] Improved clinical outcomes of 7+3 induction regimens in AML over 40 years

 Last Update: 2022-08-15
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7+3 AML

Early mortality, complete remission (CR) rates, and overall survival (OS) in acute myeloid leukemia (AML) patients treated with cytarabine in combination with anthracyclines (7+ 3) have been reported since the 1980s The extent to which OS increases with prolonged duration of first complete remission (CR1) and salvage therapy (including allogeneic hematopoietic cell transplantation) after first relapse has not been assessed; The relative contribution levels may provide some insight into the interpretation of past and current resear.

Based on this, Pr.

Research methods

The authors included 1247 patients randomized to arm 7+3 from 5 NCI and NCTN clinical trials conducted by SWOG and analyzed patients ≤65 years of age in SWOG studies, including the S8600 study (n = 530; 1980s), the S9031 study ( n = 98; 1990s), S9333 studies (n = 57; 1990s), S0106 studies (n = 301; 2000s), and S1203 studies (n = 261; 2010s), where S9031 and 9333 were combin.

In each trial, 7+3 treatments were given according to contemporaneous criteria and varied over ti.

Research result

cohort patient characteristics

Table 1 summarizes the patient characteristics in the studies analyzed by deca.

Changes in clinical outcomes over time

As can be seen from Figure 1, OS after CR1 increased during this time period, including in the multivariate regression model (Table 2), in patients treated after 2000 compared to patients treated before 2000 Multivariate hazard ratio (HR) = 43 (p < 0001); included in patients who achieved CR1, patients treated after 2000 had fewer recurrences and longer time to recurrence (Figure 2), including multivariate regression models The same is true (Table 2), multivariate HR = 40, p < 0001 (controls before 200

For patients who achieved CR1, Figure 4 and Table 3 summarize the percentage of consecutive CR1 at landmark time poin.

Relative benefit of CR and relative harm of relapse over time

At the 40 years analyzed, achieving CR1 was associated with greater OS benefit (HR = 06 before 2000, HR = 16 after 2000), although patients treated after 2000 did not benefit as much as before 2000 (in other words, In other words, HR after 2000 is more significantly closer to 1 than HR before 2000, mutual p=00

discuss

In this study cohort, overall survival of patients with AML improved significantly over the past four decades, and this improvement was observed across all intermediate endpoints, including early mortality, CR1 rate, CR1 length/time to relapse, relapse rate and OS after CR1 relap.

The improved outcomes may be related to higher chemotherapy doses, improved antibiotics, increased use of allogeneic hematopoietic cell transplantation, and the addition of novel agents, including GO and FLT3 inhibitors, to first-line, refractory, and salvage thera.

These same reasons for improved survival may also explain why the relative benefit of CR1 and the relative reduction in relapse after CR1 were less pronounced in patients treated after 2000 than in patients treated before 200 It should of course be recognized that the lack of HCT data from earlier studies also confounds these analyses, especially CR1 length, as the absence of HCT data would make it impossible to distinguish the specific role of HCT in these temporal tren.

Another is that the characteristics of patients treated with 7+3 in the above trials changed significantly over time (even if the inclusion criteria were mostly stable), and the increase in the proportion of low-risk patients, on average, may reflect the availability of low-intensity regimens, The availability of azacitidine and decitibine after 2000, in particular, may also reflect the potential for increased late selection bi.

In addition, the 7+3 regimen actually changes over time, with doses of both drugs changing over time, and multivariate analysis cannot correct for factors that are completely confounding with study/period, such as changing treatment doses to tease out individual patient contributio.

Since the introduction of response criteria such as CRp, CRi, MLFS, and CRh in the early 2000s, as contemporary trials mature and long-term analyses of their outcomes become feasible, examining their impact (relative to CR) on survival will also be very importa.

interesti.

references

Megan Othus, et .

Improved outcomes with 7+3 induction chemotherapy for acute myeloid leukemia over the past four decades: analysis of SWOG trial da.

Haematologic.

2022 Jul 1 doi: 13324/haemat.

20228076

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