All content on this site is intended for healthcare professionals only. By acknowledging this message and accessing the information on this website you are confirming that you are a Healthcare Professional. If you are a patient or carer, please visit the Lymphoma Coalition.

The Lymphoma Hub uses cookies on this website. They help us give you the best online experience. By continuing to use our website without changing your cookie settings, you agree to our use of cookies in accordance with our updated Cookie Policy

Introducing

Now you can personalise
your Lymphoma Hub experience!

Bookmark content to read later

Select your specific areas of interest

View content recommended for you

Find out more
  TRANSLATE

The Lymphoma Hub website uses a third-party service provided by Google that dynamically translates web content. Translations are machine generated, so may not be an exact or complete translation, and the Lymphoma Hub cannot guarantee the accuracy of translated content. The Lymphoma Hub and its employees will not be liable for any direct, indirect, or consequential damages (even if foreseeable) resulting from use of the Google Translate feature. For further support with Google Translate, visit Google Translate Help.

Steering CommitteeAbout UsNewsletterContact
LOADING
You're logged in! Click here any time to manage your account or log out.
LOADING
You're logged in! Click here any time to manage your account or log out.
2020-03-20T13:06:36.000Z

Depth of remission following first-line therapy | A prognostic marker in gastric mucosa-associated lymphoid tissue lymphoma

Mar 20, 2020
Share:

Bookmark this article

Mucosa-associated lymphoid tissue (MALT) lymphoma is a type of marginal zone lymphoma belonging to the indolent non-Hodgkin lymphoma (NHL) entity.1 Histopathological markers of MALT lymphoma include the presence of lymphoepithelial lesions, follicular colonization and plasmacellular differentiation.2 Although MALT lymphoma can affect any organ, gastric presentation is responsible for up to 50% of all cases.2

The impact of initial depth of remission to first-line therapy on progression-free survival (PFS) in patients with gastric MALT lymphoma has not yet been established. Barbara Kiesewetter-Wiederkehr, Medical University of Vienna, AT, and colleagues investigated patient responses to first-line therapy and subsequent relapse patterns. The study which was published in Cancers in February placed a major focus on a sub cohort of patients that had received Helicobacter pylori (H. pylori) eradication therapy.2 The Lymphoma Hub hereby presents a summary of the results.  

Introduction

Chronic H. pylori gastritis has been associated with gastric MALT lymphomagenesis, and therefore H. pylori eradication is the standard of care (SoC) for patients with the condition.3 Antibiotic treatment demonstrates favorable outcomes in patients with gastric MALT lymphoma, inducing 5-year survival rates as high as 90%. However, follow-up biopsies uncover persistent disease in around one third of patients previously classed as being in complete remission (CR).2 It has been suggested that persisting or residual disease may be affected by the level of remission following first-line treatment. Uncovering a relationship between depth of remission and patient outcome may influence the clinical management of patients with gastric MALT lymphoma.2

Study Design

  • Retrospective evaluation of all patients treated for histologically verified primary gastric MALT lymphoma at the Medical University of Vienna between 1999 and 2019
  • Outcome parameters: progression-free survival (PFS) and time to next treatment (TTNT), overall survival (OS) including cause of death
  • An objective response to first-line treatment is defined as a partial remission (PR) or complete remission (CR)
  • Patients with stable disease (SD) or no change (NC) are referred to as non-responders

Results

Patient characteristics

  • Of the 412 patients diagnosed and treated for MALT lymphoma, 137 classified for primary gastric MALT lymphoma (Table 1)
  • The majority of patients (68%) were H. pylori positive
  • Median follow-up was 56.2 months

Table 1. Baseline characteristics of gastric MALT lymphoma patient cohort

MALT-IPI, MALT lymphoma prognostic index; IQR, interquartile range

*IE, confined to the stomach

IIE, presenting with local lymph node involvement 

±IIIE, presenting with distant lymph node involvement

§IV, disseminated disease

Characteristic

% of patients (n = 137)

Sex, Female

51

Median age, years (range)

63 (22 – 85 years)

Age 70 years

28

Stage of disease-Ann Arbor

Ann Arbor IE*

Ann Arbor IIE

Ann Arbor IIIE±

Ann Arbor IV§

 

66

23

1

10

MALT-IPI (available in 122 patients)

Low risk

Intermediate risk

High risk

 

62

33

6

Further clinical features

Helicobacter pylori positive

Plasmacellular differentiation

Autoimmune disorder

Paraproteinemia

 

68

22

20

27

Median follow-up time, months (IQR)

56.2 (26.3111.6)

First-line treatment

  • The nature of, and patient responses to first-line treatment are illustrated in Tables 2 and 3 respectively
  • Due to conflicting treatment guidelines, 22 out of the 44 of H. pylori-negative patients were treated with antibiotics only
    • Overall response rates (ORR) to eradication treatment observed in H. pylori-positive versus H. pylori-negative patients: 62% vs 46%
  • The mean time to an objective response was significantly prolonged by H. pylori eradication compared to upfront systemic or local therapy: 7.6 months vs 4.3 months (p = 0.002)

Table 2. Front-line treatment approaches

H. pylori, Helicobacter pylori

Treatment

% of patients

First-line treatment overall collective (N = 137)

H. pylori eradication

Systemic treatment (chemo-/immunotherapy)

Local therapy (radiation, surgery)

Watch and wait

 

70

23

4

3


Table 3. Patient outcomes to first-line treatments

CR, complete remission; H. pylori, Helicobacter pylori; ORR, overall response rate; PD, progressive disease; PR, partial remission; SD, stable disease

Response to treatment, %

ORR

CR

PR

SD

PD

Overall collective (n = 128)

 

67

48

19

30

3

H. pylori eradication therapy (n = 93)

 

58

 

38

 

20

 

39

 

3

Systemic treatment (n = 30)

90

 

77

 

13

 

7

 

3

Local treatment (n = 5)

100

 

80

 

20

-

-

 

Patient survival outcomes

  • Patients achieving an objective response were significantly less likely to undergo second-line therapy compared to patients with SD as the best response (41% vs 63%, p=0.021)
  • TTNT did not differ significantly between patients achieving a PR and CR in any cohort

Table 4. Patient survival outcomes at a median follow-up of 56.2 months

CI, confidence interval; CR, complete response; H. pylori, helicobacter pylori; PFS, progression-free survival; PR, partial remission; SD, stable disease; TTNT, time to next treatment

*This difference remained significant after multivariate correction for MALT-IPI factors

Outcome

Overall collective (N = 137)

H. pylori eradication cohort (n = 96)

Relapse/progression, %

52

49

Median estimated PFS, months (95% CI)

34.2 (16.0–52.4)

27.6 (22.632.6)

PFS, months

Objective response

Non-responders

p

 

68.3

17.3

< 0.001

 

49.0

17.3

< 0.001

Median estimated PFS CR vs PR, months

CR

PR

p

 

94.8

28.5

0.007

 

109.4

27.6

0.020*

TTNT

Objective response

SD

p

 

47.5

15.3

0.001

 

30.3

15.4

0.008

 Long-term outcome

  • Five- and ten-year OS rates were 91% and 79% respectively
  • OS did not differ significantly between patients achieving an objective response and non-responders
  • Four patients died as a result of B-cell lymphoma:
    • Progression of MALT 302 months following initial diagnosis (n = 1)
    • Gastric bleeding (n = 1)
    • Progression of an unrelated Epstein-Barr virus (EBV)-associated B-cell lymphoma (n = 1)
    • Transformation to diffuse large B-cell lymphoma (n = 1)

Conclusions

  • The depth of remission following first-line treatment significantly correlated with length of PFS and TTNT across the entire cohort and is a useful prognostic marker
  • In contrast, OS was not influenced by the depth of remission
  • PFS was not impacted by the diagnosis of autoimmune disorders, plasmacellular differentiation or the presence of paraproteinemia
  • Limitations of this study:
    • lower than expected response rate to antibiotics in the unselected population, possibly due to the relatively large fraction of H. pylori-negative patients
    • response to eradication treatment was not correlated with translocation t(11; 18) (q21; q21) status, which has been associated with lack of response to antibiotics
  • Although the data do not support early oncological intervention to force achievement of a complete remission, the authors suggest to develop risk-stratified follow-up algorithms, which would allow to reduce the number of endoscopic controls in patients with a good response to treatment and absence other risk factors such progression, transformation or death

  1. Bacon C.M. et al. Mucosa-associated lymphoid tissue (malt) lymphoma: A practical guide for pathologists. J Clin Pathol.2007 Apr; 60(4):361–72. DOI: 10.1136/jcp.2005.031146
  2. Kiesewetter B. et al. Depth of Remission Following First-Line Treatment Is an Independent Prognostic Marker for Progression-Free Survival in Gastric Mucosa-Associated Lymphoid Tissue(MALT) Lymphoma Cancers (Basel).2020 Feb 20; 12(2). DOI:3390/cancers12020492
  3. Ruskoné-Fourmestraux A. et al. EGILS consensus report. Gastric extranodal marginal zone B-cell lymphoma of MALT. 2011 Jun; 60(6):747–58. DOI: 10.1136/gut.2010.224949

Understanding your specialty helps us to deliver the most relevant and engaging content.

Please spare a moment to share yours.

Please select or type your specialty

  Thank you

Newsletter

Subscribe to get the best content related to lymphoma & CLL delivered to your inbox